Health Technical Memorandum 2010 · Health Technical Memorandum 2010 HTM 2010 is being published in...

Health TechnicalMemorandum 2010

Part 5: Good practice guide

Sterilization

London: HMSO

© Crown copyright 1995Applications for reproduction should be made to HMSOCopyright UnitFirst Published 1995

ISBN 0 11 322188 6

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About this publication

Health Technical Memoranda (HTMs)

give comprehensive advice and

guidance on the design, installation and

operation of specialised building and

engineering technology used in the

delivery of healthcare.

They are applicable to new and existing

sites, and are for use at various stages

during the inception, design,

construction, refurbishment and

maintenance of a building.

Health Technical Memorandum 2010

HTM 2010 is being published in five

parts:

• Part 1 - Management policy -

is a summary of the information

required by non-technical

personnel responsible for the

management of sterilization

services. It discusses the various

types of sterilizer, for both clinical

and laboratory use, and also

contains guidance on legal and

policy matters, and on the

appointment and responsibilities

of personnel. It should be read

by anyone consulting this

memorandum for the first time;

• Part 2 - Design considerations

- contains information relevant

to the specification and

installation of new sterilizing

equipment. It discusses the

requirements for each type of

sterilizer and outlines the

specifications to be included in

any contract. Practical

considerations for the installation

of sterilizers are discussed,

including siting, heat emission,

ventilation, noise and vibration,

and mains services with an

emphasis on steam quality;

• Part 3 - Validation andverification - covers all aspects

of validation and periodic testing

of sterilizers. It includes detailed

schedules and procedures for

tests and checks to be carried

out for commissioning and

performance qualification, and

for subsequent periodic testing;

• Part 4 - Operationalmanagement - covers all

aspects of the routine operation

and maintenance of sterilizers,

stressing the need for a planned

maintenance programme along

with the type of records to be

kept. Advice on the safe and

efficient operation of sterilizers is

given, as well as procedures for

reporting defects and accidents;

• Part 5 - Good practice guide -

provides advice on the fatigue

life of pressure vessels, the

lethality of heat sterilization

processes, steam, contracts for

testing, and accommodation for

gas cylinders and canisters. It also

includes a comprehensive

bibliography.

The contents of this HTM in terms of

management policy and operational

policy are endorsed by:

a.

b.

c.

the Welsh Office for the NHS in

Wales;

the Health and Personal Social

Services Management Executive

in Northern Ireland;

the National Health Service in

Scotland Management

Executive.

References to legislation appearing in

the main text of this guidance apply to

the United Kingdom as a whole, except

where marginal notes indicate variations

for Scotland and Northern Ireland.

Where appropriate, marginal notes are

also used to amplify the text.

In Scotland LTSF sterilizers areconsidered to be disinfectors.

Preface

HTM 2010 gives guidance on the choice, specification, purchase, installation,validation, periodic testing, operation and maintenance of the following typesof sterilizer in use in the National Health Service:

a. clinical sterilizers:

( i ) high-temperature steam sterilizers used for processing porous loads(including instruments and utensils wrapped in porous materials);

(ii) high-temperature steam sterilizers used for processing aqueousfluids in sealed containers;

(iii) high-temperature steam sterilizers used for processing unwrappedsolid instruments and utensils;

(iv) dry-heat sterilizers (hot-air sterilizers);

(v) low-temperature steam (LTS) disinfectors and low-temperaturesteam and formaldehyde (LTSF) sterilizers;

(vi) ethylene oxide (EO) sterilizers;

b. laboratory sterilizers:

( i ) high-temperature steam sterilizersspecialised operating cycles;

(ii) culture media preparators.

used with one or more

No guidance is given on sterilization by irradiation, hydrogen peroxide, gasplasma or filtration. Users who wish to employ these processes bear theresponsibility of ensuring that the validation procedures comply with theprinciples outlined in Part 3 of this HTM and that the intended operatingprocedures will ensure an efficacious process for the different types of load.

This HTM is intended primarily as a guide for technical personnel, whetherspecialists in sterilizers and sterilization procedures or those responsible formaintenance and testing. It is also intended for those responsible for the day-to-day running of sterilizers, and will also be of interest to supplies officers,architects, estates managers and others in both the public and private sectors.

Scottish Health Planning Note 13,‘Sterile services department’, appliesin Scotland.

Detailed information on the planning and design of a sterile servicesdepartment, including the level of provision of sterilizers, is given in HealthBuilding Note 13, ‘Sterile services department’. Guidance for laboratoryinstallations can be found in Health Building Note 15, ‘Accommodation for

pathology services’.

Although this edition of HTM 2010 reflects established sterilizer technology, it isrecognised that considerable scope exists for the utilisation of emergingtechnology in the management of sterilizers. This will be kept under reviewwith the aim of introducing recommendations for such technology at theearliest opportunity so that the procedures essential for the efficient, safe andeffective operation of sterilizers can be optimised.

Most of the British Standards for sterilizers which were applicable at the time ofthe last edition of this HTM, in 1980, have been either withdrawn or radicallyrevised. Some of them, in turn, are now being replaced by European Standardswhich will be published during the currency of this edition of HTM 2010. Some

of these European Standards support new European Union Directives onmedical devices which will have a major impact on sterilization. Wherepracticable the information in this HTM has been aligned with existing oranticipated standards and advice is offered where no standard has yet beenformulated.

The sterilizers described in this HTM may not be suitable, without modification,for safely processing articles infected with Hazard Group 4 pathogens noragents, such as those associated with transmissable spongiformencephalopathies, which are unusually resistant to sterilization. Designconsiderations for sterilizers intended to process articles infected with suchorganisms are discussed in Part 2.

This part of HTM 2010 contains detailed supplementary information thatexpands upon the guidance given in Parts 1 to 4 and should be read inconjunction with them.

InformatIon about Hazard Groupsmay be found in the HSC document‘Ca tegorisation of pathogensaccording to hazard and categories ofcontainment’ (second edition 1990)compiled by the Advisory Committeeon Dangerous Pathogens.

Contents

About this publication

Preface

A The lethality of heat sterilization processes - theF 0 concept page 3

B Methods for determining therectangular pressure vessels

C Packaging for terminallyproducts page 51

fatigue lifepage 33

sterilized

D A contract for the annual testing ofsterilizers page 127

E Procedures for determining thegenerated by a sterilizer page

sound171

F Accommodation for ethylene oxide gas cylinders,manifolds and canisters

References and bibliography

page 179

of

power

page 185

Other publications in this series page 189

About NHS Estates page 190

Section A

Lethality of heat sterilization processes;

the F O concept

Contents

A1

A2A2.2A2.10

A2.11

A2.12A2.16

A2.19A2.25A2.29A2.35A2.38

A3A3.2A3.9

A4A4.1A4.2A4.3A4.11A4.15A4.17A4.23A4.27A4.34A4.45A4.49

A5

Introduction page 7

Fundamental concepts page 9How microbes die: the logarithmic order of deathConditions resulting in a non-logarithmic order ofdeathFactors influencing the nature of the survivorcurveFactors influencing the heat resistance of sporesTreatment of sterilization process microbialsurvival dataDecimal reduction valueThe temperature dependence of resistanceZ valueLethal ratesF value

Sterility page 19Sterility assuranceCalculation of F 0 values

Applications of the F 0 concept page 22GeneralControl of sterile cooling fluidF 0 controlled sterilizersMonitoring operating cyclesValidation of operating cyclesContainer cool pointLoad cool pointMicrobial challenge studiesProduct degradation and stability v cycle lethalityProduct stabilityCycle development studies

Test methods page 28

Glossary page 30

Bibliography page 31

A1.0 Introduction

A1.1 There are several, well established, time temperature relationships forthermal sterilization methods which are regarded as equally acceptable (see Part3 of this HTM, Table 8, page 41). Clearly temperatures other than those shown,when maintained for an appropriate time, will also be capable of producing asterile product.

A1.2 For a moist heat sterilization process, we can expect a particular time ata particular temperature to have a predictable lethal effect against astandardised population of organisms. If we choose particularly resistantorganisms and assume they are present in numbers in excess of that likely to beencountered in real product we can define standard exposure conditions whichwill always yield a sterile product in a correctly operated sterilizer. Actualexposures can then be related to these standard exposure conditions.

For example, in the laboratory it is possible to produce conditions where thetime to attain a pre-selected sterilization temperature, and the time to cool toambient temperature after sterilization, is so short that it may be disregarded: aso-called “square wave exposure” system. This will enable very accuratedeterminations of the thermal resistance of micro-organisms under well definedconditions, and from several such determinations at different temperatures anaccurate determination of the change in thermal resistance with temperature tobe made.

Operational sterilizer cycles do not produce this rapid heating and cooling buthave relatively slow temperature changes. The product is thus exposed totemperatures somewhat below the chosen sterilizing temperatures forconsiderable periods. It is apparent that there will be some lethal effect onmicro-organisms during the heating and cooling phases of any particularsterilization cycle since microbial death occurs over a wide range oftemperatures, albeit at different rates.

The F 0 concept recognises this and allows us to takeobtained during the heating and cooling phases.

account of the lethality

A1.3 For heat sensitive products it is desirable to minimise the heat treatmentgiven to the product and reduce the energy input to a level which, whileproviding adequate assurance of sterility, will minimise the degradation of theproduct. Because the F 0 concept allows us to take account of the inactivationof micro-organisms throughout the cycle, not just during the sterilization holdperiod, we can thus obtain a cycle with the required lethality but withminimum thermal degradation.

A1.4 In summary, optimisation of thermal sterilization processes may beachieved by means of the F method which uses a knowledge of the lethality ofthe particular process at different temperatures to assess the overall lethality ofthe cycle and express this as the equivalent exposure time at a specifiedtemperature.

A1.5 F is defined as the equivalent time in minutes at 121.1°C to produce agiven sterilization effect.

A1.6 Where the specified temperature is 121.1°C (250°F) and the Z value is10°C the term F 0 is used.

The F 0 value of a saturated steam sterilization process is the lethality expressedin terms of the equivalent time in minutes at a temperature of 121ºC deliveredby that process to the product in its final container with reference to micro-organisms possessing a Z value of 10.

The total F 0 value of a process takes account of the heating up and coolingdown phases of the cycle and can be calculated by integration of lethal rateswith respect to time at discrete intervals.

A1.7 The F 0 method may be used for assessment, or control, of processeswhere difference in temperature is the only factor influencing the efficacy ofthe cycle. For example, it may be applied to the steam sterilization of aqueousfluids in sealed containers but it is not applicable to steam sterilization ofporous loads where air removal is also a key factor and failure to achieve directcontact with Dry Saturated Steam can lead to failure, regardless of whether therequired temperature was achieved within the load.

A1.8 Similar concepts are also used fordepyrogenation by exposure to dry heat.

dry heat sterilization processes and for

A1.9 There are a number of pre-requisites which it is necessarybefore the use of the F 0 method is appropriate. These include:

to consider

• the efficacy of the sterilization process under consideration IS dependentonly on temperature eg air removal is not critical. Thus in a porous-loadsteam sterilizer where impaired air removal can allow air to persist inrandom locations throughout the load, and where it may be present insufficient quantity to impair sterilization, the use of the F 0 method forcycle control or monitoring IS inappropriate;

• the sterilizer to be used has cycle control which is adequate to ensurethat production cycles consistently reproduce the conditions establishedduring validation. F 0 monitoring of a process may not be used to justifythe use of a sterilizer which demonstrates excessive temperature variationwithin the load or poor reproducibility from cycle to cycle etc;

• temperature profile studies/validation studies have been conducted toestablish the uniformity of conditions throughout load and to identify thelocation of those parts of the load which are slowest to heat up andfastest to cool down;

• the loading composition and pattern of production cycles is controlledwithin the limits established during validation to ensure that the resultsobtained remain valid;

• production controls and bioburden studies are adequate to maintain aknown, low level, of microbial contamination and the thermal resistanceand temperature dependence (D and Z values respectively) of the mostresistant contaminant(s) are known or the assumed values are inaccordance with the Pharmacopoeial recommendations.

A2.0 Fundamental concepts

A2.1 In order to use the F0 concept correctly it is important to understand thefacts, definitions and assumptions on which the model is based. It has becomecommon place to use certain functions and terms in the analysis andinterpretation of data on the effect of physical or chemical stress on microbialsurvival. These terms are discussed below.

How microbes die: the logarithmic order of death

A2.2 Organisms which die as a result of an imposed stress die in an orderly,and predictable, manner. This can be represented as survivor curve, showingthe number of organisms still living at various times after the beginning ofexposure to the stress condition.

A2.3 The order of death is, in principle, the same for all multicellularorganisms. The survivor curve remains constant for as long as individuals canrecover from that length of exposure; then as the first individuals die, thefrequency of death rapidly Increases until only a few very resistant organismsremain, and they succumb shortly after the majority of the population (seeFigure A1). In a unicellular organism the individual is dead when a single celldies, whereas in multicellular organisms the death of one cell is not likely to killthe Individual. The multicellular organism will survive until enough cells havebeen killed to cause death.

Figure A1 Arithmetic survivor curve for multicellular organisms

A2.4 Whichever multicellular organisms are tested, for example insects orplants, and whatever the lethal stress, the survivor curve remains essentially thesame. This was accepted as universally true for all organisms until the early1900s when workers such as Harriet Chick [see Chick (1908)] showed that inan homogeneous culture of a single strain of bacteria the cells died at aconstant rate when exposed to a particular lethal stress.

A2.5 It was apparent that these bacteria were dying in a manner which wassomewhat unexpected. This may be illustrated by taking as an example thesurvival of microbial spores subjected to heat stress. An experiment may bedevised in which all factors other than the heating time are held as constant aspossible. If a number of biological indicators, each bearing a known number ofbacterial spores, are subjected to a thermal sterilization process, at apredetermined temperature for various increments of exposure time, and thenthe survivors on each indicator enumerated, the data obtained shows thenumber of colony forming units remaining viable after each exposure time.

A2.6 A survivor graph can be prepared showing the number of survivors as afunction of the length of heating time. Both the number of survivors and thetime may be plotted on an arithmetic scale (see Figure A2).

Unicellular bacteria

Figure A2 Arithmetic survivor curve for unicellular bacteria

A2.7 Alternatively the number of survivors may be plotted on a logarithmicscale as a function of time on the arithmetic scale, which is referred to as asemi-log survivor curve (see Figures A3 and A4). While both the arithmetic andsemi-log survivor curves accurately represent the death of bacteria the latter ismore useful in sterilization studies where interest is concentrated on the rate ofdestruction as the number of survivors approaches zero.

Multicellular organisms

Figure A3 Semi-log survivor curve for multicellular organisms

A2.8 It is usual to use the latter approach since in sterilization studies we areinterested in the rate of destruction as the number of surviving micro-organismsapproaches zero, which is best shown using a logarithmic plot.

Unicellular bacteria

Figure A4 Semi-log survivor curve for unicellular bacteria

A2.9 Experience has shown that the semi-log survivor curve for heat stressoften approximates to a straight line for part or all of the survivor curve.However there are many recorded instances where deviations from the “ideal”straight line condition occur (see Figure A5).

Figure A5 Microbial survivor curves showing typical deviations from the linear model;curve a is a theoretical linear survivor curve; curve b shows an initial “shoulder”followed by a linear survivor curve; curve c shows an initial increase in count,“activation”, followed by a linear survivor curve; curve d shows an initial linearsurvivor curve followed by a decreasing rate of kill, “tailing”; curve e shows thesigmoidal survivor curve often encountered in experimental determinations.

Conditions resulting in a non-logarithmic order of

death

A2.10 Typical survivor curves for bacterial spores exposed to moist heatsterilization processes are shown in Figure A5 in which the logarithm of thenumber of surviving organisms is plotted against time and various types ofresponse are illustrated:

•

•

•

•

•

Curve a - exponential - constant fraction of the population is inactivatedper unit time;

Curve b - shows an increasing death rate after an initial period wherethere was little or no inactivation - a “shoulder”;

Curve c - initial activation (increase in population) followed by a constantdeath rate;

Curve d - decreasing death rate with a low number of highly resistantorganisms surviving for a prolonged period - "tailing";

Curve e - a sigmoidal survivor curve of the type frequently encountered inexperimental determinations of resistance. This type of survivor curve maybe regarded as a composite of elements of the survivor curves describedabove.

Factors influencing the nature of the survivor curve

A2.11 There are a number of factors which have a significant effect on thenature of the survivor curve. Workers such as Moats et al (1971) have discussedthese factors in detail. Some of the key factors can be summarised as follows:

••

•

Growth index. During recovery there are many instances when not allviable spores will germinate and outgrow within a short time period. Thepercentage of those present which do germinate and grow immediatelyon incubation is referred to as the growth index. The growth index variesboth with the species of bacterial spore and the cultural conditions inwhich it was grown and is to be recovered. It may be as high as 100%,for example for Bacillus subtilis, but may be as low as <1%, for examplefor Bacillus stearothermophilus. Sublethal heating may increase (activate)or decrease (deactivate) the growth index and give rise to non-linearsurvivor curves. [see Favero (1967), Finley and Fields (1967)] Theinteraction of activation and inactivation on the thermal treatment ofheat resistant dormant spores of B stearothermophilus can be describedmathematically. [see Shull et al. (1963)]

Cell clusters. The usual method of counting the number of survivingbacteria is by the plate count method which gives the number of coloniesdeveloped from a known volume of suspension inoculated onto thesurface of solid growth medium. The number of colonies is equal to thenumber of bacteria present only when each colony arises from a singlecell.

When the cells are in clusters, for example Staphylococcus spp., or inchains, for example Streptococcus spp., one colony may represent a largenumber of cells. All the time there are one or more surviving cells withinthe aggregation a colony will be formed and death therefore becomesevident only when the last cell is dead. Such clusters “die” likemulticellular organisms and show convex survivor curves (see Figures A3and A5, curve b).

l Cell age. It has been demonstrated that young cells, that is, theexponential growth phase of a culture, are more susceptible to bothchemical and physical stress than old cells from the stationary phase of aculture. Furthermore if old cells are transferred to a new environmentthey do not all begin to grow at the same time and a culture develops inwhich both old and young cells coexist leading to heterogeneousresistance and concave survivor curves (see Figure A5, curve d).

l Mixed populations. Where more than one strain or species is present,with different resistances to the lethal stress being imposed, a non-linearsurvivor curve, typically of concave form, will arise (see Figure A5,curve d).

Factors influencing the heat resistance of spores

A2.12 Any assessment of thermal resistance of micro-organisms must involveconsideration of those factors which may affect the thermal resistance.

A2.13 These factors include the species and strain of organisms to beconsidered; its physiological state, which will in part depend on its immediatecultural history, the manner in which it is presented to the sterilization process,for example the suspending menstruum; and the recovery conditions which areused in an attempt to grow the organism after exposure to the process; as wellas the exposure conditions used, for example whether dry heat or moist heat(direct contact with dry saturated steam or being in an aqueous solution) wasused, and the exposure temperature. [see Russell (1971)]

A2.14 The nature of the product also affects the thermal resistance ofcontaminating organisms; the protective effects of various salts andcarbohydrates in solution are well documented in the literature.

A2.15 The influence of changes in the manufacturing environment and/orprocess on the nature and extent of contaminating micro-organisms must alsobe considered.

Treatment of sterilization-process microbial survival

data

A2.16 A mathematical approach to the resistance of bacteria to thermaldeath is required to allow calculation of equivalent lethality. Two factors needto be considered; the thermal resistance of the micro-organism at a particulartemperature and the change in that resistance which occurs with changes intemperature.

These two factors are analogous to the rate constant and temperaturecoefficient of a chemical reaction, respectively.

A2.17 Spore inactivation in moist heat may be considered as amonomolecular first order reaction, that is where the rate of reaction is governed by the concentration of the reactant, in this case the bacterial spores.

This may be expressed as

where t = time,Ca = spore concentrationk = a reaction rate constant at constant temperature

Then ( log Ca

0 - log Ca ) = k ( t - t0 )

where the superscript 0 indicates initial conditions

A2.18 A semi-logarithmic plot of concentration versus time will yield astraight line of slope k. k has dimensions of time-1. The negative reciprocal ofthe rate constant k is equivalent to the number of minutes required toinactivate 90% of the organisms present, that is a 1 log reduction. This value isreferred to as the D value and, as stated, mathematically it is inverselyproportional to the inactivation rate constant k

D = 2.303/k.

Decimal reduction value (D value)

A2.19 The D value is used as a measure of the resistance of a defined micro-organism to a defined sterilization process. It is a convenient way to describethe slope of a linear semi-log survivor curve.

A2.20 More particularly it may be defined as the extent of exposure, understated conditions, necessary to produce a 90%, or 1 log, reduction in thebacterial population (see Figure A6). It is usually stated in minutes, except forsterilization processes using ionising irradiation where it is given in kiloGreys(units of absorbed radiation dose).

Figure A6 Decimal reduction value

A2.21 For moist heat sterilization processes it is often given a subscript toindicate the temperature at which it was determined, for example D121. Although this in itself is insufficient definition of the conditions under whichthe determination was made to allow valid comparison.

A2.22 The D value is highly specific to the experimental conditions underwhich it was determined. Even apparently minor changes in experimentalprocedure, for example incubation temperature, recovery medium can have adramatic effect on the apparent D value.

A2.23 The D value is only relevant to the survivor curve when the survivorcurve is truly a straight line over the range of population values of interest,including the “probability” zone.

A2.24 It is not necessary to construct a survivor curve to determine D valueThe determination may be done by a replicate unit method involving fractional-unit-negative (FN) data. A number of replicates are heated for a certain timeand the number viable and the number sterile are determined. [see Pflug andSchmidt (1968)]

Then where r = total number,p = growth,q = sterile,U = time in min,N0 = initial population per replicate unitNU = population per replicate unit after time U,

thenNU = logn(r/q) = 2.303 log (r/q)

and

D =duration of treatment (min) .

log initial no - log final no of spores

=U .

log N0 - log NU

The temperature dependence of resistance

A2.25 A common measure of the temperature dependence of a chemicalreaction is the Q10 value. This is defined as the change in reaction rate constantk for a 10°C change in temperature:

A2.26 For most chemical reactions Q10 has a value of about 2, but for sporeinactivation in moist heat Q10 ≈ 10 to 18 and for spore inactivation in dry heatQ10 ≈ 2.2 to 4.6.

A2.27 Other measures of temperature dependence include the Arrheniusequation;

k = A ex p ( - E A ( RT) -1 )

where k = the reaction rate constant;A = the frequency factor;E A = the activation energy;R = the universal gas constant;T = the absolute temperature.

A2.28 However, the temperature dependence of reaction rates for spores isgenerally expressed as a Z value,

where

or

Z value

A2.29 The Z value is a measure of the change of inactivation rate withtemperature. It is the slope of a plot of D value on a logarithmic scale againsttemperature on an arithmetic scale (see Figure A7).

A2.30 The Z value allows comparison of the lethal effect of heating atdifferent temperatures. [see Bigelow (1921)]

A2.31 As originally defined Z is numerically equal to the number of degreesFahrenheit change in temperature required to reduce the D value by 90%, or 1log. Considerable confusion, and error, can be caused where the temperaturescale used is not specified. Although values are now usually given in °C caremust be taken when using published data, for example from the officialcompendia, to note whether the D value is quoted in °F or °C.

A2.32 The mathematical relationship with the D value can be expressed as:

A2.33 It should be noted that, the greater the Z value, the greater theincrease in temperature which is required to give a tenfold decrease in D value.Hence the assumption of a Z value higher than in fact exists will give anadditional margin of safety. The Z value assumed for most thermophiles, suchas Bacillus stearothermophilus, is 10°C.

A2.34 The straight-line relationship holds good only over a limitedtemperature range for an homogenous culture of a single strain of micro-organisms. Mixed cultures give a non-linear relationship, but in practice onesub-population, either by virtue of its resistance or its prevalence, will becontrolling with regard to attainment of sterility.

Lethal rates

A2.35 The usefulness of the temperature dependent model lies in being ableto calculate the lethality over a range of temperatures, which will include thoseexperienced during heating-up and cooling-down of a load in a steam sterilizer.

A2.36 The relative lethality at a temperature , Texp, compared to the known

lethality at a particular reference temperature , Tref, is dependent on the Z value.

Thus, the lethality L is given by the equation

Lethality factors forand for any Z value

anycan

temperature deviation from ther reference temperaturebe calculated using this formula (see Table A1).

A2.37 A new variable F, the thermal death time can be defined. The changein F with temperature is analogous to the change in thermal resistance (Dvalue) with temperature and both are dependent on the Z value. Plots of log Dversus temperature and log F versus temperature both have slope Z:

F value

A2.38 The F value expresses heat treatment in terms of the equivalent effectof a stated time at some stated temperature for a particular Z value, that is tosay that the F value is the equivalent time in minutes at 121.1°C (250°F) for anorganism of specified Z value.

A2.39 F0 is the F value when Z is 18°F (10°C):

where t is the chosen time interval, and T is the temperature in the container.

Note For dry heat F values, F is equal to the time in minutes at 176°C (350°F).

Table A1 Lethality factors for a Z value of 10°C

Temperature Lethality Temperature Lethalitydifference factor difference f a c t o r °C minutes* °C minutes*

- 2 0 . 0

- 1 9 . 0 0.0126 +19.0 83.180

- 1 8 . 0 0.0159 +18.0 66.070

- 1 7 . 0 0.0200 +17.0 52.480

- 1 6 . 0 0.0251 +16.0 41.690

- 1 5 . 0 0.0316 +15.0 31.620

- 1 4 . 0 0.0398

- 1 3 . 0 0.0501

- 1 2 . 0 0.0631

- 1 1 . 0 0.0794

- 1 0 . 0 0.1000

- 9.0 0.1259

- 8.0 0.1585

- 7.0 0.1995

- 6.0 0.2512

- 5.0 0.3162

- 4.5 0.3548

- 4.0 0.3981

- 3.5 0.4467

- 3 . 0 0.5012

- 2 . 5 0.5623

- 2.0

- 1.5

- 1.0

- 0.5

0.0100

0.6310

0.7079

0.7943

0.8913

0.0 1 . 0 0 0

+20.0

+14.0

+13.0

+12.0

+11.01

+10.0

+ 9.0

+ 8.0

+ 7.0

+ 6.0

+ 5.0

+ 4.0

+ 3.0

+ 2.8

+ 2.6

+ 2.4

+ 2.2

+ 2.0

+ 1.8

+ 1.6

+ 1.4

+ 1.2

+ 1.0

+ 0.8

+ 0.6

+ 0.4

+ 0.2

0.0

100.000

25.120

19.950

15.850

12.590

10.000

8.318

6.607

5.248

4.169

3.162

2.512

1.995

1.905

1.820

1.738

1.660

1.585

1.514

1.445

1.380

1.318

1.259

1.202

1.148

1.096

1.047

1.000

Lethality L is given by

* Lethality factor is given in minutes equivalent at the reference temperature

A3.0 Sterility

A3.1 In order to utilise the F0 method it is first necessary to decide on the

extent of treatment which will be necessary to provide the required level ofassurance that the product is sterile. Several different definitions are in commonuse.

Sterility assurance

A3.2 If the survivor curve is extrapolated beyond log100, that is one survivingorganism, we reach a region of “probability” of finding a single survivingorganism. For example at log10[-1] we expect to find, not 0.1 organismssurviving in every sample but, one in every ten samples with a surviving micro-organism.

We can thus determine from the survivor curve a theoretical probability of anyone unit of product being non-sterile.

A3.3 The European standard, EN556, in common with a definition in theEuropean Pharmacopoeia, states that a product may be regarded as sterilewhen the theoretical level of not more than one micro-organism is present in1 x 10 6 sterilized units of the final product.

A3.4 This calculation may be based on data, obtained by investigation, onthe extent and resistance of microbial contamination immediately prior tosterilization (the Bioburden) or on a theoretical contamination of 106 micro-organisms per unit of product presumed to be of a type having known highresistance to the process, for example bacterial spores. In the latter case thecycle is often referred to as a “12D” or “overkill” cycle and was first proposedby Esty and Meyer (1922) for processing low-acid canned food products.

A3.5 The British Pharmacopoeia in Appendix XVIII 'Methods of Sterilization'states: “For aqueous preparations sterilized by heating in an autoclave thepreferred combination of temperature and time is a minimum of 121ºCmaintained throughout the load during a holding period of 15 minutes.”However, it goes on to say: “Other combinations of time and temperature maybe used provided that the process chosen delivers an adequate level of lethalitywhen operated routinely within the established tolerances.”

A3.6 In Annex 2, 'Guidance on application of the F0 concept to aqueouspreparations.’ the British Pharmacopoeia sugggests that "In general for aqueouspreparations a microbiologically validated steam sterilization process thatdelivers, in total, an F0 value of not less than 8 to every container in the load isconsidered satisfactory.”

A3.7 In certain circumstances, however, use of a steam sterilization processthat delivers, in total, an F0 of less than 8 may be considered justifiable, forexample where the product is especially heat sensitive. The nature of processesdelivering an F0 of less than 8 is such that great care must be taken in order toensure that adequate assurance of sterility is consistently achieved. It isnecessary not only to validate the process microbiologically but also to performcontinuous, rigorous microbiological monitoring during routine production todemonstrate that the microbiological parameters are within established

tolerances so as to give a theoretical level of not more than one living micro-

organism per 106 containers in the final product.

A3.8 The European Pharmacopoeia also states that the recommended methodfor parenteral products is moist heat sterilization at a minimum of 121°Cmaintained throughout the load for a minimum of 15 minutes. Other timetemperatures can be used but the crucial requirement is delivery of anadequate level of “lethality” to the product. The use of F0 is recognised with anF0 of 8 being the usually acceptable minimum. It is emphasised that thisrequires a low pre-sterilization bioburden and the absence of heat resistantspores.

Calculation of F0 values

A3.9 Reliabl e F0 value calculations are simply achieved with modernmicroprocessor based control and monitoring systems. However F0 values canbe calculated manually, and many of the available computer programs employessentially similar methods:

a. Graphical method. In the graphical method F reference paper is used onwhich the lethal rate per minute, at particular temperature, is representedby length on the vertical axis. The horizontal axis has a correspondingarithmetic scale for time such that the area of a rectangle delineated bythe ordinate 121.1°C and a length corresponding to one minute on theabscissa is equal, by definition to an F0 of one. The cumulative area underthe curve as the cycle progresses represents the cumulative lethality of theprocess (see Figure A8). In practice the temperature profile is plotted andthe area under the curve determined using a planimeter. The areameasured is then converted to an F0 value using the scale of the Freference paper.

b. Summation method. In the summation method the lethal rate at eachspecific temperature is calculated or read from a table (see Table A1) andmultiplied by the time for which that temperature persisted. The valuesobtained for each temperature are summed to give the overall F0 valuefor the cycle.

A3.10 The accuracy of the integration is affected by a number of factors.These include:

· the choice of time interval between successive temperaturemeasurements. BS 3970 Part 2 specifies a maximum interval of twoseconds;

· whether the minimum, maximum or average temperature during thechosen time interval is used. (Since the method is an approximation basedon summing discrete data to represent continuous data there will alwaysbe some error, which may be positive or negative; each may be correctfor different purposes);

· the location of the sensor(s) from which the temperature is read and theadequacy of the validation of sensor location;

· should be used only over the temperature range for which Z has beendetermined. The Z value for any micro-organism does not remainconstant over all possible temperatures. Therefore any particular lowertemperature limits for the integration need not be set since, for a Z valueof 10, F0 values below 105°C make so little contribution. For example, 40minutes exposure at 105°C is equivalent to one minute at 121°C.

Figure A8 Graphical determination of F0 values. The ordinate scale (temperature) ofF-reference paper is proportional to the lethal rate so that the area beneaththe curve is a measure of the F value. The cumulative values during thecooling stage are not used for sterilizer control but may be used in monitoringto provide an accurate assessment of the overall lethality delivered by thesterilization cycle. Within each box the figures in italics indicate the F0 valuecalculated for that time-temperature rectangle. The lower figures indicatethe cumulative F0 value through the cycle. The F0 controller, set to provide anF0 value of 9, initiates the cooling stage at point A. The total monitored F0

value of the cycle is 11.99.

A4.0 Applications of the F0 concept

General

A4.1 Part 3 of this HTM states that if a fluid sterilizer is fitted with an F0

integrating system, then the recorder should be capable of computing andprinting values of F0 for each channel with integration times no greater than2 s. This is also a requirement of BS 3970: Part 2.

Control of sterile cooling fluid (in a steam sterilizer

for fluids in sealed containers)

A4.2 It is a requirement that if the coolant is derived from a water or steamservice and is intended to come into contact with the load containers, theoperating cycle must expose the coolant to sufficient heat to ensure that it isfree of microbial contamination by the end of the holding time. This is checkedby calculating an F0 value for the heat treatment received by the coolant. If thetest recorder is not capable of calculating F0 both BS 3970 and Part 3 of thisHTM recommend the following procedure:

a. from the measured temperatures, identify the point during the heat-uptime at which the coolant temperature first reaches 108°C. Note thetemperature (T°C) at subsequent one minute intervals until the end of theholding time;

b. for each measurement, calculate the incremental F 0 (∆ F 0 ) from thefollowing equation:

where T is the lowest temperature of the coolant water for each oneminute time interval

c. the F0 value is the sum of all ∆ F0.

The test should be considered satisfactory if the F0 for the coolant is not lessthan 8 minutes.

F0 controlled sterilizers - Control of operating cycles

in steam sterilizers for fluids in sealed containers

A4.3 The operating cycle for steam sterilizers used to process aqueous fluidsin sealed containers may be divided into several stages.

1. heat up (and, where necessary, air removal) - the chamber atmosphereattains the required temperature;

2. equilibration time - all parts of the load attain or exceed the minimumtemperature of the sterilization temperature band;

Table A2 Permitted ranges for F0 values

F0 value Permitted rangeindicated by for F0 valuessterilizer determinationunder by the referencetest instrument*

1 1 to 105

15 15 to 15.7

30 30 to 31.5

* The reference instrument is described inTest method 2.

3. holding time - all parts of the load are maintained at a temperaturewithin the sterilization temperature band;

4. cooling stage - the load is cooled to a temperature at which it will besafe to handle.

A4.4 Stages 2 and 3 may be controlled by one of the following:

a. adjustable timers of an automatic controller in conjunction withtemperature sensors within the active chamber discharge and withincontainers of the load;

b. a simulator control system;

c. an F0 system.

A4.5 Provision for adjustment of the equilibration time (stage 2) is necessaryand may be achieved by one of the following:

a. an operator adjustable timer on the instrument panel;

b. a simulator control system;

c. an F0 integrating system.

A4.6 When an F0 control system is fitted, the control function should belimited to the Initiation of the cooling stage (stage 4) once a selected F 0 valuehas been attained.

A4.7 In addition to the minimum requirement of two temperature sensors(see 13.1.4 of BS 3970 Part 1) two further temperature sensors shall beprovided for use in two load containers.

A4.8 The control system shall be designed to integrate from the temperaturessensed within containers of the load at selected locations at time intervals notexceeding 2 seconds.

A4.9 The range of F0 values selectable shall include 1 to 30.

A4.10 When tested in accordance with Test method 1, the Individual valuesof F0 determined using the reference instrument shall be within the rangesstated in Table A2 for each of the F0 values indicated by the sterilizer undertest.

Monitoring operating cycles in steam sterilizers for

fluids in sealed containers

A4.11 For aqueous products in sealed containers temperatures are measured(with thermocouples or RTDs) throughout the heating and cooling stages aswell as during the sterilization hold period. The slowest container to heat andthe fastest container to cool may be used to determine the minimum lethalityreceived by the load. these locations are often found in different locations.

A4.12 Determination of the maximum temperatures in the load may also benecessary for thermolabile products where deterioration may be a problem.

A4.13 It is essential that during commissioning and validation it is establishedthat the position of containers which need to be monitored remains consistentfrom cycle to cycle. A sterilizer where the slowest part of the load to reachtemperature is found in different parts of the load on successive cycles is notsuitable for control or monitoring by F0 values and is in urgent need of skilledattention. For air-ballasted sterilizers this may involve additional requirementson monitoring the circulation of the chamber atmosphere to ensure that thelocation of the cool point remains constant.

A4.14 Calculation of the F0 value delivered by a process may be estimatedfrom the lowest temperature-time curve registered from the containers in theload. The process is satisfactory if the registered F0 value is within the minimumand maximum limits established during validation.

Validatio n of operating cycles in steam sterilizers for

fluids in sealed containers

A4.15 The use of F0 control or monitoring systems places additionalrequirements on the validation process.

A4.16 As described in Part 3 of this HTM, paragraph 8.4 'Sterilizer functionusing a full load' '... the temperature of all sites monitored within the load ......shall be within 1°C of each other throughout stage 3'. This requirement appliesregardless of whether an F0 system is used.

Container cool point

A4.17 Container mapping is necessary to determine the container cool point.Container mapping studies should be conducted prior to conducting loadedchamber heat penetration studies in order to determine the position within theliquid-filled container which is slowest to attain temperature.

A4.18 Small volume containers and those of cylindrical form where thelength:diameter ratio is large are the least likely to demonstrate a detectablecold spot.

The number of thermocouples within the container should be sufficient tomonitor the upper, middle and lower layers of the central region of thecontainer. Using an excessive number of temperature probes may introducesignificant errors in the determination.

A4.19 The profile point requiring the longest exposure time to equilibratewith the chamber temperature should then be used in subsequent F0 studiesand monitoring (but see later for degradation/product stability considerations).

A4.20 Suitable container entry systems for the insertion of temperatureprobes into sealed containers are described in part 3 of this HTM (Figure 3,

p 40)

A4.21 Independent measuring equipment should be to the standarddescribed in part 3 of this HTM, Chapter 6.

A4.22 The test should be carried out as described in part 3 of this HTM for athermometric test for a full load (see paragraph 14.10) except that the loadshould be containers of the type and number to be used in practice and filledwith the product to be sterilized or a suitable substitute with similar thermalcharacteristics, (see paragraph A4.31 below).

Load cool point

A4.23 It is necessary to determine the coolest point within a specified loadtype and configuration of load. Cool points arise because of varied rate of heattransfer throughout the load and studies are needed to ensure that the coolpoints are identified so that they may be exposed to sufficient heat lethality.

A4.24 The study is carried out in the same manner as the performancequalification described in part 3 of this HTM (see paragraphs 8.13 to 8.28performance qualification, pp 57 to 59)

A4.25 Similar studies may be used to identify those containers which attaintemperature maxima or most prolonged exposure to the equilibriumtemperature for product degradation and/or stability studies.

A4.26 The F0 value for the process may then be determined by integratingthe lethal rates throughout the heating process using one of the methodspreviously described.

Microbial challenge studies

(See also part 3 of this HTM paragraphs 8.29 to 8.36, pp 59 - 60)

A4.27 Biological challenges may be used during validation studies in order todemonstrate the process lethality provided by the sterilization cycle. Calibratedbiological indicators used for this purpose act as bioburden models and can beused in obtaining data to calculate F0 values delivered by the cycle or tosupplement physical temperature measurement, for example fromthermocouples.

A4.28 The number of spores to be used in the BI can be calculated from thefollowing formula

A4.29 Designated liquid-filled containers are inoculated with the indicatororganism by injecting an aliquot of a calibrated spore suspension into thesuspending menstruum to provide the calculated concentration of spores. Thecontainers chosen should be those previously established by temperaturemeasurement as having the lowest delivered lethality.

A4.30 The suspending menstruum should be the product to be sterilizedunless this contains preservatives, antimicrobials or other substances whichinhibit the growth of the indicator micro-organisms.

A4.31 If it is necessary to use a product substitute it should be selected tohave similar physical characteristics to the product this should include heatcapacity (specific heat), density, viscosity, thermal conductivity.

A4.32 Great care needed when using inoculated product to minimise the possibility of contaminating the production environment.

A4.33 Microbial challenge studies should be conducted concurrently withheat penetration studies.

Product degradation and stability versus cycle

lethality

A4.34 When heat-sensitive thermolabile products are to be sterilized it isimportant that adequate assurance of sterility is not obtained at the expense ofproduct degradation or stability.

A4.35 For sterilization the temperature dependence of the process isdescribed by the Z value, that is the change in temperature required to give atenfold change in the rate of microbial kill. Increasing or decreasing thetemperature of the process requires a corresponding decrease or increase inexposure time to maintain the same cycle lethality or F0 value.

A4.36 For any given temperature, microbial death and chemical degradationtake place at different rates. The relationship between time and temperaturewhich exists for microbial lethality cannot be extrapolated to the productdegradation reaction.

A4.37 If the degradation reaction is not altered significantly by the change intemperature the extent of degradation will increase as process (exposure) timeis extended. Conversely, if the degradation reaction is highly temperaturedependent (high activation energy) a decrease in temperature may more thancompensate for the increase in time, resulting in less degradation.

A4.38 The key variable is the activation energy, EA. If the activation energyfor the chemical degradation reaction is lower than that of the microbial deathcurve, that is it is less temperature dependent, then it can be assumed that adecrease in sterilization temperature will result in greater product degradation.

A4.39 Furthermore it cannot be assumed that sterilization cycles ofequivalent lethality, but which differ with regard to time and temperature, willyield product of equal quality.

A4.40 The assumption that degradation reactions follow first-order reactionkinetics is probably a good approximation in most cases where a single activedrug product is contained in the solution.

A4.41 Experience has shown that a decrease in sterilization temperature canhave a marked deleterious effect on product and its long term stability.

A4.42 Sterilization of glucose solutions in plastic containers may require asterilization temperature in the range 115-118°C in order to protect thethermolabile container. The increased time required for sterilization comparedwith a traditional cycle at 121°C used for similar solutions in glass bottlesresults in a noticeable increase in caramelization.

A4.43 The activation energy of the lethal reaction for bacterial spores with aZ value of 10°C is high (typically around 60 kcaI/moIe) compared to most first-order liquid-phase decompositions. Thus products that degrade with heat aremore affected by an increase in time than an increase in temperature. Forexample, expressed as a Z value the temperature effect of the degradation ofglucose would have a Z value of about 33°C.

A4.44 The use of F values based on the Z value of the most resistantcontaminating organism found during bioburden studies rather than anassumed Z value of 10°C may be necessary for particularly thermolabileproducts. Great care is needed in the application of this technique because ofthe inherent variability of microbial contamination and the rigorous processcontrol and monitoring needed to minimise this.

Product stability

A4.45 Product stability may also be related to degradation duringsterilization. Chemical reaction kinetic studies on many products indicate thatproduct stability over the desired shelf life can be extrapolated from the extentof degradation measured just after sterilization. In some cases a degradationproduct formed during sterilization triggers subsequent deterioration and thespecific factors affecting the formation of the degradation product would needto be investigated.

A4.46 Both microbial lethality and degradation are cumulative with respect totime and temperature, so variations in the heating and cooling phases of thecycle will affect the extent of degradation, and thus product stability, as well aslethality.

A4.47 Degradation and stability studies should consider the entire cycle andnot just the dwell time. These effects are more pronounced for products wherethe degradation reaction has a lower activation energy.

A4.48 F0 values are generally calculated from the coolest part of the load. Fordegradation and stability purposes the hottest part of the load is of moreconsequence. The entire range of temperature and time experiencedthroughout the load must be recorded in order to substantiate degradation andstability claims.

Cycle development studies

A4.49 Determination of F0 values is often of value in the development ofappropriate operating cycles for steam sterilization of both fluids in sealedcontainers and wrapped goods and porous loads. However, since temperaturemeasurement alone cannot reliably detect failure to obtain direct contact withdry saturated steam, it is not practicable to use F0 values for monitoring orcontrolling porous load cycles.

The use of F0 values for porous load cycles should be limited to determiningsuitable sublethal cycles for biological challenge studies.

A5.0 Test methods

Test for F0 control compliance

Apparatus

A5.1 Glass bottle, of nominal capacity 1 litre, complying with DIN 58363.

A5.2 Independent F0 reference instrument, as described in section F.

Procedure

A5.3 Install the reference instrument.

A5.4 Place 1 litre of cold water in the bottle. Insert the two temperaturesensors of the F0 control system and the sensor of the reference instrument sothat the sensing points of all three are at about 85% of the bottle depth andover the approximate centre of the bottom of the bottle. Seal the bottle.

A5.5 Select the required F0 value on the control panel and perform a cycle inwhich automatic control is terminated manually immediately at the beginningof stage 4. Note the value of F0 shown by the reference instrument.

A5.6 Repeat the procedure described in paragraph A5.5 twice.

A5.7 This test procedure shall be carried out for F0 values of 1, 15 and 30.

A5.8 Calculate the mean of the three replicate values for each setting of F0

control and check for compliance with the values given in Table A2.

Test for performance of reference instrument

Apparatus

A5.9 Temperature regulated heat source capable of being controlled at agiven temperature within 0.10°C in the range 115°C to 126°C.

A5.10 Thermometer traceable to national standards to include the range100°C to 130°C complying with BS 593 and graduated at intervals of 0.1ºC.

A5.11 Temperature logging device computing F0 values of the sensor(s) withintegration at least every 2 s and means of print out, together with suitabletemperature sensor(s).

A5.12 Stopwatch.

Procedure

A5.13 Install the sensor(s) into the temperature regulated heat source.

A5.14 Adjust the heat source so that it maintains a temperature of121±0.1°C.

A5.15 Allow the equipment to integrate F0 for 15 minutes timed with thestopwatch. Note the indicated F0 value.

A5.16 Repeat with the temperature source maintained at 115±0.1°C for 30min.

A5.17 Repeat with the temperature source maintained at 126±0.1°C for 10min.

A5.18 The replicate F0 values obtained at 121°C shall lie within the range14.66 to 15.34.



Glossary

D value

Z value

F 0

The D value (or Decimal Reduction Value) is a measure of the resistance of a micro-organism to aparticular type of sterilization process. It is the value of the appropriate parameter of the process(duration or absorbed dose) required to reduce the number of viable micro-organisms to 10% ofthe original number.

In connection with sterilization by heating in an autoclave the D value is expressed by the timeminutes at a defined temperature (the temperature is often shown as a subscript, for example

D 1 2 1) .

in

In connection with sterilization by heating in an autoclave the Z value relates the heat resistance ofa micro-organism to changes in temperature. The Z value is the change in temperature required toalter the D value by a factor of 10.

A quantity, measured in minutes, used to determine the efficacy of an operating cycle andequivalent to a continuous period at a temperature of 121.1°C for an organism with a Z value of10°C.

Bibliography

Laboratory Manual for Food Canners and Processors. 1968, Vol 1 Microbiologyand Processing, National Food Processors Association Research Laboratories,Westport, Connecticut. AVI Publishing Company.

Tucker G S and Clark P. 1989, Computer Modeling for the Control ofSterilization Processes. Technical memorandum No 529. Campden Food andDrink Research Association.

Pflug I. 1982 Textbook for an Introductory Course in the Microbiology andEngineering of Sterilization Processes. Minneapolis. Environmental SterilizationLaboratories.

Hersom and Holland 1980 Canned Foods: Thermal Processing andMicrobiology. 7th Edition. London. Churchill Livingstone.

Stumbo C R 1973 Thermobacteriology in Food Processing. 2nd Edition. NewYork. Academic Press.

Validation of steam sterilization cycles. Technical Monograph No 1. 1978,Philadelphia, Parenteral Drug Association.

Section BMethods for determining the fatigue life ofrectangular pressure vessels

(This section has been withdrawn pending clarificationof copyright.

Please refer to BS 3970 Appendix C.)

Previous pageis blank

33

Section C

Packaging for terminally sterilized products

Contents

C1C1.3C1.6C1.11C1.14C1.16C1.17

C2

C2.2C2.4

C2.7C2.8

C2.9

C2.31C2.32

C3C3.9

C3.62C3.68

C3.92

C3.98C3.101C3.103C3.108C3.110

Introduction page 55Sterilization processProduct applicationsResponsibilityGeneral performance requirementsPackaging operationsQuality control

Regulatory requirements andstandards page 58SafetyMedicinal productsC2.6 Guide to Good Manufacturing

PracticeConsumer protectionActive Implantable Medical Devices Regulations1992Medical Devices RegulationsC2.12 General requirementsC2.14 Requirements regarding design and

constructionGlass containers EEC Directive 75/107British and European standards

Design considerations page 65Compatibility with sterilization processC3.11 Moist-heat/steam processorsC3.12 Sterilizers for wrapped goods and

porous loadsC3.21 Sterilizers for unwrapped instruments

and utensilsC3.24 Aqueous products in sealed

containersC3.32 Low-temperature steam and

formaldehydeC3.36 Ethylene oxideC3.49 Hot-air sterilizersC3.53 IrradiationCompatibility with labelling systemCompatibility with requirements for asepticopeningCompatibility with the contentsC3.92 Medical devicesC3.95 Medicinal productsC3.97 Laboratory productsToxicityBiocompatibilityPreservation of sterilityStorage and transport of sterile packsNumber of layers of packaging materialC3.120 Primary and secondary packagingC3.121 Secondary packaging

C4 Packaging materials andsystems page 78

C4.5 Sterilization compatibilityC4.5 Steam sterilization

C4.5 Wrapped goods andporous loads

C4.7 Fluids in sealed containersC4.8 Dry heatC4.11 LTSFC4.14 IrradiationC4.15 Ethylene oxide

C4.19 Bacterial barrier propertiesC4.27 Materials used in packaging

C4.29 TextilesC4.35 Papers and non-wovensC4.45 Synthetic materials and laminatesC4.51 Polyethylene (polythene)C4.58 PolyesterC4.60 Polyvinyl chloride (PVC)C4.63 Polypropylene and polycarbonateC4.68 NylonC4.69 Glass containersC4.73 Metals

C4.76 Single-use packagingC4.78 Paper or textile wrapsC4.93 Paper bags, paper/plastic pouches

C4.93 FoldingC4.98 Self-sealC4.100 Heat seal

C4.114 Glass containersC4.117 Ampoules - fusion sealC4.128 Vials and bottlesC4.129 Screw capsC4.133 Crimp caps

C4.136 Re-usable packagingC4.136 TextilesC4.142 Containers for solid goods

C4.142 Impermeable or unventedcontainers

C4.143 Open-topped trays andperforated containers

C4.146 Instrument orientation traysC4.148 Dressings drums

C4.150 Re-usable rigid containersC4.187 Glass containersC4.190 Vials and bottles

C4.190 CleaningC4.192 Inspection

C4.196 Screw capsC4.201 Crimp caps


C5

C5.2C5.8C5.9C5.17

C6

C7

C7.1

C7.60

C8C8.1C8.3

C8.14C8.20

C8.36

C8.49C8.53C8.58

Purchase, quality control andstorage page 101PurchaseSpecificationQuality controlStorage

Validation of packaging systems page 104

Facilities and environmental control forpackaging operations page 107Packaging operationsC7.3 General requirementsC7.11 Facilities for packaging operations

C7.11 CleaningC7.16 Cleaners’ roomC7.20 Sterile Services Department

- SSDC7.24 Linen roomC7.31 Packing roomC7.42 Sterilizer loading areaC7.44 Post-sterilization areaC7.48 Processed goods storeC7.54 Materials store

Packaging equipmentC7.60 Heat sealersC7.65 Overseal crimpersC7.70 Screw cappers - controlled torqueC7.72 Ampoule sealers

C7.72 Manual sealing

Packaging operations page 114Routine operation, control and monitoringDocumentationC8.5 Packaging instructionsC8.6 Batch packaging recordsC8.10 Packaging records for single packsC8.11 Batch numberingLabellingControl of the packaging operationC8.27 Heat-sealing equipmentC8.32 Glass containersQC testsC8.39 Pin holesC8.43 Inspection of sealsC8.46 Packaging for sterile medicinal

productsProcess indicatorsSterile product releaseOperator training

C9C9.1C9.8C9.10C9.25C9.28C9.36C9.42

Storage and distribution page 120Shelf lifeDistribution of sterilized suppliesStorage of sterile suppliesHandling sterile packsTransport and distributionStorage in clinical areasPackaging for return of used items forre-processing

Glossary of terms page 124

C1.0 Introduction

C1.1 This section discusses the factors which should be considered in theselection and use of packaging for terminally sterilized products, that is, thosematerials which are sterilized in their packaging.

Packaging for medical equipment which has been cleaned,decontaminated/disinfected and serviced ready for return to use is not includedin this guidance.

C1.2 It does not consider those products which are sterilized and thenaseptically packed in sterilized packaging materials nor does it cover packagingof terminally sterilized components to be used in aseptic manufacturing.

Sterilization processes

C1.3 Because the product is sterilized in its packaging it is necessary that thepackaging maternal is compatible with the sterilization process to be used.

C1.4 The sterilization processes included are those which are generallyavailable for use either directly or through a sub-contractor. It does not includerequirements for new processes which are currently under development or atan early stage of their introduction for practical use. This would include, forexample, those systems employing gaseous or plasma phase peracetic acidand/or hydrogen peroxide.

C1.5

a.

Sterilization processes included are:

Steam - for clinical use (see HTM 2010 Part 1, paragraph 2.1 (a)):

(i) for wrapped goods and porous loads;

(ii) for aqueous fluidsin rigid containers;- in flexible containers;

(iii) for unwrapped instruments and utensils- externally supplied steam;- internally generated steam;

b. Steam - for laboratory use (see HTM 2010 Part 1, paragraph 2.1 (b)):

c. Low-temperature steam and formaldehyde. Note. The packagingmaterials, systems and procedures described are also suitable for use withdisinfection processes intended for use with wrapped goods, for exampleLow Temperature Steam Disinfectors (LTS);

d. Ethylene oxide

e. Dry heat (hot air)

f . Ionising irradiation (gamma and beta)

Product applications

C1.6 The sterile products for which packaging is considered include:

• medical devices and surgical Instruments:

- primarily those products, including re-usable instruments, utensils andtextiles, which are processed by Sterile Service Departments, includingunits directly serving operating theatres (although the same principlesapply to other manufacturing systems which have a wide range ofproduct specifications produced singly or in small numbers. Onlypassing reference is made to high speed automated packagingsystems.);

- re-usable instruments processed in clinics and general practices (dentaland medical);

• pharmaceutical manufacturing of sterile products;

• laboratory product manufacturing, for example culture media formicrobiology;

• discard (or make-safe) prior to disposal of potentially infective material.

C1.7 Consideration is given to materials and systems for both single-use andre-usable packaging.

C1.8 Single-use packaging includes, for example, ampoules, single-tripbottles, paper bags, paper/plastic pouches & reels, paper wraps, vacuumformed trays, etc.

C1.9 Re-usable packaging includes, for example, multiple-trip bottles,procedure trays, sterilization containers, textile wraps, etc.

C1.10 This guidance section also makes reference to labelling, storage anddistribution giving both guidance and particular requirements necessary toensure compliance with extant regulations.

Responsibility

C1.11 Part 1 of HTM 2010 (paragraph 1.15 (h)) Identifies the procedures forproduction, quality control and safety as a major responsibility of management.

C1.12 The provisions of this section should be reviewed by those responsiblefor the management of sterile production and adapted to local circumstances(for example taking into consideration the nature of the product, the volume ofproduction, the sterilization process(es) available etc).

C1.13 It should be used as the basis for the development of written policies,specifications and procedures to be used in the control of sterile production.

General performance requirements

C1.14 The purposes for which packaging is used are:

• to contain the product;

• to permit sterilization of the packaged product;

• to protect the product from deterioration and damage;

• to maintain the sterility of the product through distribution and storageto the point of use;

• to prevent contamination of the product.

C1.15 In addition the packaging must:

• permit identification of the number and type of product contained, thelot number, the manufacturer and the expiry date (by labelling);

• include specification of storage conditions which the packaging isdesigned to withstand;

• provide any necessary instructions for the correct use of the product (bylabelling and/or instruction sheets);

• present the product in a mannerimmediately before use.

which allows it to be removed aseptically

Packaging operations

C1.16 The procedures and controls implemented for packaging operationsmust be designed to ensure that:

• each product produced is in the correct type of pack;

• each pack is correctly and effectively sealed;

• each pack is correctly labelled with all the necessary information.

Quality control

C1.17 The nature of packaging for terminally sterilized products is such that:

• it is not possible to test the packaging on finished product in a mannerwhich permits its subsequent distribution for use;

• it is not possible to test any one sample for all necessary characteristics;

• it is not possible to test each pack immediately before use to ensure thatthe packaging has performed correctly throughout sterilization,distribution and storage.

C1.18 Adequate control of the quality of packaging can only be obtainedthrough a comprehensive programme including:

• design, and design verification;

• specification of packaging procedures;

• validation of packaging procedures;

• control of purchased material;

• control and monitoring of the packaging process;

• training for all who produce, handle or use sterile packs.

C1.19 Labelling is an essential part of packaging and procedures are requiredto ensure that particular care is taken to avoid labelling errors.

C1.20 The importance of proper control over all aspects of the packagingprocess cannot be over-emphasised. When products such as medical devices ormedicinal products are presented wrongly labelled, contaminated, or damagedtheir use can cause serious adverse effect and may, in extreme cases, be lethal.

C2.0 Regulatory requirements andstandards

C2.1 So far as requirements for packaging, including labelling, are concerned,the chief areas of legislation with which managers should be familiar are thoseconcerned with safety, consumer protection, medicinal products, medicaldevices, active implantable medical devices and in vitro diagnostics.

The legislation relevant to sterilizers is also discussed in HTM 2010 Part 1,Chapter 3, to which reference should be made.

Safety

C2.2 Manufacturers have two specific obligations under the Health andSafety at Work etc. Act 1974:

a. to take all reasonably practicable steps to ensure that their products havebeen designed and manufactured so as to be safe when used for theintended purpose;

b. to ensure that persons who use their product in further manufacturingand retailing operations have adequate information and advice abouthow the products should be used to ensure safety.

C2.3 There is also a more general requirement under common law to protectall persons involved with the use of the product.

Medicinal products

C2.4 Where a packaging material or system is used to contain a medicinalproduct the licensing provisions of the Medicines Act 1968 apply.

Further information may be found in ‘Guidance to the NHS on the licensingrequirements of the Medicines Act 1968’ published by the Medicines ControlAgency.

C2.5 The Medicines (Standard Provisions of Licences and Certificates)Amendment Regulations 1992 (Sl 1992/2846) give statutory force to theEuropean Commission document ‘The rules governing medicinal products inthe European Community Volume IV Guide to Good Manufacturing Practice formedicinal products.’

Guide to Good Manufacturing Practice for medicinal products

C2.6 The principles and detailed guidelines of good manufacturing practicedeal with a number of aspects of packaging including:

• Documentation, which should include:

- a formal, written specification for packaging materials;

- formally authorised packaging instructions for each product, pack sizeand type;

- a record kept for each batch or part batch processed.

• Purchase, handling and control should be treated in the same manner asstarting materials with particular attention paid to printed material;

• Packaging operations should be designed to minimise the risk of mix-upsby the inclusion of a line clearance procedure and special care should beexercised to avoid mislabelling.

The packaging should be verified as being of the correct type, clean and in thecorrect quantity and there should be suitable on-line control and monitoring toverify the adequacy of the packaging operation.

Consumer protection

C2.7 Part 1 of the Consumer Protection Act 1987 implements Directive85/374/EEC (the Product Liability Directive) and provides for compensation tobe paid to persons suffering injury from a defective product. The implications ofthis legislation are discussed in HTM 2010 Part 1 (paragraphs 3.26 to 3.28inclusive).

Active Implantable Medical Device Regulations 1992

C2.8 The Active Implantable Medical Devices Regulations 1992(Sl/1992/3146) implements Council Directive 90/385/EEC. Schedule 2,paragraph 7 of these regulations requires active implantable medical devices tobe designed, manufactured and packed in a non-reusable packaging accordingto procedures which are sufficient to procedures which are sufficient to ensurethat:

a. the device is sterile when placed on the market;

b. if handled in accordance with conditions as to storage laid down by themanufacturer, the device remains sterile until the packaging is removedand the device is implanted.

Medical Devices Regulations

C2.9 The Medical Devices Regulations 1994 (Sl/1994/3017) implementsCouncil Directive 93/42/EEC of 14 June 1993 concerning Medical Devices andcame into effect on 1 January 1995.

C2.10 Regulation 11 concerns the procedure for systems and procedurepacks and requires, inter alia, that any person who puts devices bearing the CEmarking together, within their intended purpose and within the limits of usespecified by their manufacturers, in order to place them on the market as asystem or procedure pack, shall draw up a declaration by which he states thathe has packaged the system or procedure pack and supplied relevantinformation to users incorporating relevant instructions from the manufacturers,and that the whole activity is subjected to appropriate methods of internalcontrol and inspection.

C2.11 The Essential Requirements described in Annex 1 (of the Directive)include a number of specific requirements for packaging and labelling whichare summarised below.

General requirements

C2.12 The devices must be designed, manufactured and packaged in such away that they are suitable for the functions specified by the manufacturer.

C2.13 The devices must be designed, manufactured and packed in such away that their characteristics and performances during their intended use willnot be adversely affected during transport and storage taking account of theinstructions and information supplied by the manufacturer.

Requirements regarding design and construction

C2.14 The devices be designed, manufactured and packed in such a way asto minimise the risk posed by contaminants and residues to the personsinvolved in the transport, storage and use of the devices and to the patientstaking into account the intended purpose of the product.

C2.15 The devices and manufacturing processes must be designed in such away as to eliminate or reduce as far as possible the risk of infection to thepatient, user and third parties.

C2.16 Devices delivered in a sterile state must be designed, manufacturedand packed in a non-reusable pack and/or according to appropriate proceduresto ensure that they are sterile when placed on the market and remain sterileunder the storage and transport conditions laid down, until the protectivepackaging is damaged or opened.

C2.17 Packaging systems for non-sterile devices must keep the productwithout deterioration at the level of cleanliness stipulated and, if the devicesare to be sterilized prior to use, minimise the risk of microbial contamination;the packaging system must be suitable taking account of the method ofsterilization specified by the manufacturer.

C2.18 The packaging and/or label of the device must distinguish betweenidentical or similar products sold in both sterile and non-sterile condition.

C2.19 Each device must be accompanied by the information needed to use itsafely and to identify the manufacturer, taking into account the training andknowledge of the users.

C2.20 This information comprises the data on the label and the data in theinstructions for use.

C2.21 As far as practicable and appropriate, the information needed to usethe device safely must be set out on the device itself and/or on the packagingfor each unit or, where appropriate, on the sales packaging.

C2.22 If individual packaging of each unit is not practicable the information must be set out in the leaflet supplied with one or more devices.

C2.23 Instructions for use must be included in the packaging for every device.By way of exception, no such instructions for use are needed for devicesclassified in Class I or IIa if they can be used safely without any suchinstructions. The majority of, but not all, products produced in hospital basedsterilization units would fall into this category, for example re-usable surgicalinstruments which are in Class I. Exceptions include implants, and may includedevices intended for use on skin wounds that have breached the dermis. Incase of doubt reference should be made to the classification criteria given in

Annex IX of the directive or advice sought from the competent authority(Medical Devices Agency, DoH).

C2.24 Where appropriate is information should take the form of symbols.Any symbol or identification colour used must conform to the harmonisedstandards. In areas for which no standards exist, the symbols and colours mustbe described in the documentation supplied with the device.

C2.25 The label must bear the following particulars:

a. the name and trade address of the manufacturer;

b. the details strictly necessary for the user to identify the device and thecontents of the packaging;

c. where appropriate, the word STERILE;

d. where appropriate, the batch code, preceded by the word LOT, or theserial number;

e. where appropriate, an indication of the date by which the device shouldbe used, in safety, expressed as the year and month;

f. where appropriate, an indication that the device is for single use;

g. if the device is custom made, the words “custom made device”;

h. if the device is intended for clinical investigations, the words "exclusivelyfor clinical investigations";

i. any special storage and/or handling conditions;

j. any special operating instructions;

k. any warnings and/or precautions to take;

l. year of manufacture for active devices other than those covered by e. Thisindication may be included in the batch or serial number;

m. where applicable, method of sterilization.

C2.26 If the intended purpose of the device is not obvious to the user themanufacturer must clearly state it on the label and in the instructions for use.

C2.27 Wherever reasonable and practicable, the devices and detachablecomponents must be Identified, where appropriate in terms of batches, toallow all appropriate action to detect any potential risk posed by the devicesand detachable components.

C2.28 Where appropriate the instructions for use must contain the followingparticulars:

a. information to avoid certain risks in connection with implantation of thedevice;

b. the necessary instructions in the event of damage to the sterile packagingand where appropriate details of appropriate methods of re-sterilization;

c. if the device is reusable, information on the appropriate processes toallow re-use, including cleaning, disinfection, packaging and, whereappropriate, the method of sterilization of the device to be re-sterilized,and any restriction on the number of re-uses.

C2.29 Where devices are supplied with the intention that they be sterilizedbefore use, the instructions for cleaning and sterilization must be such that ifcorrectly followed the device will still comply with the general requirementsspecified in Section I, Annex I of the directive.

C2.30 The instructions for use must also include details allowing the medicalstaff to brief the patient on any contra-indications and any precautions to betaken.

Glass containers EEC Directive 75/107

C2.31 Capacity tolerances for bottles specified as measuring containers weredefined in the Directive and are summarised in Table C1.

Two methods of capacity verification were specified, the Standard deviationmethod and the Mean range method.

British and European standards

C2.32 The rapid development in European Standards, which are required tobe adopted as national standards by all European members of the EuropeanCommittee for Standardisation (CEN), is largely due to the role that suchstandards have in demonstrating compliance with legislation implementingEuropean Directives.

CEN is recognised by the European Union as a competent body for theadoption of harmonised standards.

C2.33 For the purpose of the European Directives on Medical Devices andActive Implantable Medical Devices a harmonised standard is a technicalspecification (European standard or harmonisation, document) adopted, on amandate from the European Commission, by CEN.

C2.34 There is a presumption of compliance to the essential requirements ofthe Directive for devices which are in conformity with the relevant harmonisedstandards the references of which have been published in the Official Journal ofthe European Communities.

C2.35 A number of standards are in preparation which are relevant topackaging and labelling of terminally sterilized products.

The following list is not exhaustive. The standards discussed are in variousstages of preparation, those marked * are finalised and published. All ENstandards are available in the UK as British Standards; there is now a dualnumbering system so that EN *** will be numbered as BS EN ***.

C2.36 EN 1041 Terminology symbols and information provided with medicaldevices - Information supplied by the manufacturer with medical devices

This standard specifies the information to be supplied by the manufacturer ofmedical devices necessary to comply with the requirements of the Directive.

C2.37 EN 980 Terminology symbols and information provided with medicaldevices - Graphical symbols for the labelling of medical devices

Table C1 Capacity tolerances for bottlesas measuring containers

Nominal Capacity tolerancescapacity as %

C (ml) of C in ml

50 - 100 - ±3

100 - 200 ±3 -

200 - 300 - ±6

300 - 500 ±2 -

500 - 1000 - ±10

1000 - 5000 ±1 -

This standard defines a number of symbols to be used in labelling medicaldevices. The use of these symbols will both facilitate provision of all theessential information on small packs and minimise the need for multi-linguallabelling.

C2.38 EN 868 series Packaging materials for sterilization of wrapped goods

This standard is presented in a series of separate parts. The first part specifiesthe general requirements for packaging materials to be used for medicaldevices which are to be terminally sterilized and provides requirements,guidance and test methods for the validation of packaging materials andsystems.

The subsequent parts of the standard specify requirements for a variety ofpackaging materials and systems. Conformity with the specified requirements inthese parts of the standard may be used as one means of demonstratingcompliance with some, or all, of the requirements of Part 1.

C2.39 EN 867 series Non-biological systems for testing sterilizers

This series of standards specifies the requirements for chemical indicators usedin testing sterilizers. Part 2 of the standard specifically addresses theperformance requirements for process indicators, whether used independentlyof, or printed on, labels or packaging materials. Detailed specifications aregiven for performance criteria relevant to all the sterilization processesconsidered in this Section (see paragraph C1.5).

C2.40 EN 724 Guidance on the application of EN 29001 and EN 46001 andof EN 29002 and EN 46002 for non-active medical devices

This standard provides guidance on suitable methods and procedures, includingaspects of packaging, for the manufacture of medical devices in conformitywith the requirements of the Quality System standards which may be used todemonstrate compliance with the requirements of the Directive.

C2.41 EN 550* Sterilization of medical devices - Validation and routinecontrol of ethylene oxide sterilization

This standard specifies requirements for the development, validation, processcontrol and monitoring of the sterilization of medical devices using ethyleneoxide and gives guidance on means by which these requirements may be met.The importance of packaging in the correct functioning of an ethylene oxidesterilization process is recognised.

C2.42 EN 552* Sterilization of medical devices - Validation and routinecontrol of sterilization by irradiation

This standard specifies requirements for the development, validation, processcontrol and monitoring of the sterilization of medical devices using ionisingradiation and gives guidance on means by which these requirements may bemet. The importance of specifying and controlling packaging from validationthrough to routine batch control is emphasised.

C2.43 EN 554* Sterilization of medical devices - Validation and routinecontrol of sterilization by moist heat

This standard specifies requirements for the development, validation, processcontrol and monitoring of the sterilization of medical devices using moist heat.

The methods used are based on monitoring physical factors and control of thepackaging is an essential part of the system.

C2.44 EN 1174 series Sterilization of medical devices - estimation of thepopulation of micro-organisms on product

This standard describes methods for determining the extent of microbialcontamination on products, including packaging, prior to sterilization.

C3.0 Design considerations

C3.1 The manufacturer of the sterile product is responsible for adopting adesign for the pack which is suitable for its intended purpose.

C3.2 However, in many cases the design of the packaging material and/orsystem may be controlled by the manufacturer of the packaging materialand/or packaging system and sold as suitable for a particular range ofapplications.

C3.3 The choice of such a pre-designed, commercially available packagingsystem does not absolve the sterile product manufacturer from theresponsibility for ensuring that:

• the design of the packaging system, including the selection of materials,is suitable in all respects for the intended application (see Chapter C6)

• the packaging system as received from the supplier is in conformity withthe specification against which the choice was made (see Chapter C5)

• the production facilities, including the skills of production personnel, arecompatible with the packaging system chosen and have thedemonstrated capability to fill, seal and sterilize the packaging inaccordance with the instructions provided by the manufacturer of thepackaging system, (see Chapters C7 - C9).

C3.4 The packaging is required to fulfil a number of functions. These may besummarised as: “to minimise the safety hazard to the manufacturer, user orpatient arising from interaction of the product with its environment under theconditions of sterilization, transport, storage and use as specified by theproducer of the packaging system and/or sterile product.”

C3.5 The design should include consideration of at least the following:

• the compatibility of the packaging with the sterilization process;

• the compatibility of the packaging with the labelling system;

• the compatibility of the packaging with the users’ requirements at thepoint of use, for example aseptic opening;

• the sensitivity of the pack contents to particular risks, for exampleirradiation, moisture, mechanical shock, static discharge.

• the compatibility of the packaging with the contents, for example themedical device or medicinal substance, in order that the packaging hasno adverse effect on the medical device or vice versa;

• the protection provided by the packaging against adverse environmentalinfluences which may reasonably be anticipated, for example mechanicalshock, vibration, chemical or microbial contamination;

C3.6 The emphasis to be given to each of these considerations will bedifferent for each of the various sterile products manufactured but,compatibility with the sterilization process and the subsequent protectionagainst microbial contamination are paramount in providing the user with asterile product.

C3.7 In many cases historical data may be used to provide satisfactoryevidence that the packaging is suitable for its intended purpose wherepackaging to the same specification has previously been used satisfactorily for aparticular product, or one that is similar in all essential respects.

C3.8 The design documentation should include details of the product to bepackaged, the sterilization process to be used, the storage and transportconditions as well as the specification of the packaging materials and processesto be used.

Compatibility with the sterilization process

C3.9 There are two important aspects to sterilization compatibility:

a. the ability of the packaging material to permit the attainment of therequired conditions for sterilization in the process with which it isintended to be used;

b. the ability of the packaging material to withstand the sterilization processwithout deterioration which adversely affects its protective performance.

C3.10 Both attributes should be demonstrated.

Moist-heat/steam sterilization processes

C3.11 For effective sterilization by moist heat all parts of the load should bein contact with water or saturated steam at the required temperature for therequired time.

Sterilizers for wrapped goods and porous loads

C3.12 Items to be sterilized, other than aqueous products in sealedcontainers, should be packaged in a pack which allows removal of air andpenetration of steam but which prevents recontamination after sterilization

C3.13 This is normally achieved by the use of materials which are permeableto air and steam but have an effective maximum pore size which is smallenough to exclude microbial contamination under the specified storage andtransport conditions.

C3.14 This includes wrapping in porous materials, the use of rigid containerswhich are fitted with filters or valves, or a combination of these methods.

C3.15 Effective sterilization requires complete permeation of the porousmaterials with the moisture and heat of the steam. This may occur rapidly orslowly and depends, inter alia, on the size and density of the pack, the methodof air removal, the nature of the porous material etc.

C3.16 With packaged solid, hollow or fibrous products air may becometrapped, randomly, in the sterilizer chamber and load. The microbial lethality ofelevated temperatures under dry and moist conditions are vastly different. Thepresence of air can cause an unacceptable impairment of the sterilizationprocess.

C3.17 Unpredictable air retention is of particular concern with porouswrapping materials. Hence for effective sterilization of wrapped goods andporous loads it is important to employ a sterilization process which incorporatesforced air removal prior to the sterilization stage.

C3.18 Preliminary tests on the product and its packaging in order todetermine the levels and rates of change of pressure, temperature and vacuumwhich start to cause unacceptable changes in the performance qualities of themedical device and/or its packaging may be necessary.

C3.19 Performance qualification should be performed on the introduction ofnew or modified packaging unless equivalence either to a validated referenceload or to previously validated packaging has been demonstrated.

C3.20 Materials used for packaging should be compatible with thesterilization process not only in permitting passage of steam and air as requiredby the process but also in not contributing any other inhibitory factors. Forexample they should not generate gases which could mimic the presence ofretained air and restrict the penetration of steam.

Sterilizers for unwrapped instruments and utensils

C3.21 Sterilizers not intended for use with wrapped goods, for example bowland instrument sterilizers, and small transportable electrically heated sterilizersrely on steam flow to remove air. Although the air may eventually be displacedfrom wrapped loads the process is slower and less predictable than whenforced air removal is used.

C3.22 The only packaging suitable for unwrapped instrument and utensilssterilizers are “instrument orientation” trays which are constructed of openmesh or with sufficient ventilation holes to ensure that they present no barrierto air removal and steam penetration.

C3.23 BS 3970 Part 4 requires that load containers for transportable sterilizersshould be designed to permit free draining of condensate and penetration ofsteam by perforation of appropriate surfaces. The perforated surfaces shouldhave not less than 10% of their area as uniformly distributed perforations, eachperforation being at least 20 mm2.

Aqueous products in sealed containers

C3.24 Sealed glass or plastics containers containing aqueous solutions permitmoist heat sterilization of the contents by virtue of the moisture present in theproduct.

C3.25 The container must have a gas-tight seal if the composition of thecontents is not to be modified by evaporation of water from the contents orthe ingress and condensation of steam from the sterilizer chamber.

C3.26 The container must be able to withstand the considerable internalpressures which will be generated during the sterilization process. This increasein pressure arises from the volumetric expansion of the container beinginsufficient to compensate for the volumetric expansion of the liquid, theincreased vapour pressure of the liquid and the increased pressure of theheated air in the vacuity.

C3.27 The pressure generated in a correctly filled 1 litre bottle when it isheated to 121°C may exceed 8 bar.

C3.28 Plastic containers, -particularly those made of polymers which undergoa reduction in tensile strength at the temperatures used for steam sterilization,are often only suitable for use in sterilizers which include air or gas ballasting toincrease the pressure throughout the cycle and thus restrain the container from

bursting. A similar approach may be used to sterilized devices used as packaging.for example pre-filled syringes.

C3.29 The safety of operators will be at serious risk from the violent failure ofcontainers and dispersal of their contents if the containers are removed fromthe sterilizer at too high a temperature (see HTM 2010 Part 3 paragraph14.20 d).

C3.30 The use of unsealed containers to avoid this problem is unacceptable.Not only is the composition of the contents subject to unpredictable changes,but liquids such as molten agar might still be boiling violently. Splashes fromhot liquids of high thermal capacity can cause serious burns.

C3.31 Containers which are “unsealed” but plugged with porous material, orhave the cap in place but left loose, that is not screwed tightly closed, may alsobecome unsafe at elevated temperature. The evaporation of water fromresidues of the contents which boiled over during the early stages of thecooling process can effectively seal the container” It is important to emphasisethat these are not theoretical considerations but represent a real hazard whichhas, in the past, caused injury to a number of personnel.

Low-temperature steam and formaldehyde

C3.32 The basic considerations for packaging for this process are similar tothose for steam sterilizers for porous loads and wrapped goods.

C3.33 However, the thermal characteristics (both the thermal capacity andthermal conductivity) of the packaging can be of importance:

a . Materials which are slow to attain the required temperature may promotethe polymerisation of the formaldehyde gas.

b. Materials of high thermal capacity promote the formation of excessivequantities of condensate which also may adversely affect the sterilizationprocess.

C3.34 In addition, the extent to which the packaging material will absorb andadsorb both moisture and formaldehyde gas may affect the efficacy of theprocess.

C3.35 In general packaging should be kept to the minimum compatible withadequate protection for the product and the maintenance of sterility.

Ethylene oxide

C3.36 The packaging should be designed to allow removal of air andpenetration of both steam and ethylene oxide and it should be demonstratedthat the specified sterilization process does not affect adversely the functioningof the packaging.

C3.37 Impervious packaging materials are unsuitable for ethylene oxidesterilization.

C3.38 There are a considerable number of different ethylene oxidesterilization processes ranging from those employing pure ethylene oxide atsub-atmospheric pressures to those which use a mixture of ethylene oxide andcarbon dioxide at pressures of several bar.

C3.39 The nature of the process, including the rate of air removal and thenature of the humidification stages used, will influence the suitability ofpackaging to be used in the process.

C3.40 A sterilization process that employs a high moisture content andseveral large and rapid changes in pressure may affect the strength of packageseals, with a consequent loss of integrity, whereas. package seals of the sametype would have been perfectly satisfactory for a process employing lessextreme conditions.

C3.41 The extent to which the packaging absorbs moisture may have a majorinfluence on the efficacy of the process and must be considered before asatisfactory humidification stage can be demonstrated.

C3.42 The extent to which the packaging absorbs or adsorbs ethylene oxide,and its permeability to ethylene oxide may have a major influence on theefficacy of the process and the subsequent aeration process used to remove thepotentially toxic residuals.

C3.43 Process control is also a concern since packaging material that hasbecome dehydrated may absorb excessive moisture during the conditioningphase; if this possibility was not recognised during validation the achieved cyclelethality may be adversely affected.

C3.44 The use of cartons (shelf packs, transit cartons) may be convenient forhandling product but increase the post-sterilization level of ethylene oxideresiduals, the necessary humidification time and the length of the gas exposurestage of the cycle (by inhibiting gas penetration). All the packaging which isintended to go into the sterilizer must be compatible with the process.

C3.45 The standard on validation of ethylene oxide sterilization processes (seeEN 550) includes the requirement that the packaging specification be part ofthe definition and documentation of the sterilization process. The validationreport should include or reference details of product sterilized, includingpackaging specification and load patterns in the sterilizer.

C3.46 It is therefore necessary that product used for physical andmicrobiological performance qualification studies should be packaged in anidentical manner to that to be used routinely when they are presented forsterilization.

C3.47 The introduction of a new, or altered, packaging material or systemrequires validation. Physical and microbiological performance qualificationstudies should be performed on the introduction of new or modifiedpackaging, although demonstration of equivalence to a previously validatedpackage would satisfy this requirement.

C3.48 Many of the packaging materials for hospital use are the same asthose for use in steam sterilizers because of similar permeability requirements;however, the lower temperatures involved in the process permit a wider rangeof materials to be used.

Hot-air sterilizers

C3.49 The thermal conductivity, specific heat and ability to withstandtemperatures of 165°C, 175°C or 185°C (depending on the process used) forextended periods, without deterioration which impairs the utility of thepackaging, are obvious considerations.

C3.50 The packaging does not need to be porous since the heat transfernormally takes place by conduction.

C3.51 However, in sealed packaging the contents of the pack when heatedcan exert a considerable pressure and may be sufficient to rupture thepackaging material or its seals.

C3.52 Vented packaging systems that allow pressure equilibration may besuitable for use in hot air sterilizers which operate with a chamber atmospherewhich has been filtered through a bacteria retentive filter. This is particularlyimportant during the during the post-sterilization cooling stage.

Irradiation

C3.53 The standard for validation of radiation sterilization processes (EN 552)requires that the process specification should include descriptions of thedimensions, density and orientation of the product within the packaging, aswell as the pattern for the loading of product within the container to be usedto transport the packs through the irradiator. This should be established anddocumented before commencing performance qualification studies.

C3.54 The orientation of the product during irradiation is one of the factorsensuring uniformity of dose and the ability of the packaging to maintainconsistent orientation of the product must be considered.

C3.55 The density of the packaging, and hence its “transparency” to theradiation to be used may be an important consideration, particularly in the caseof electron beam irradiation.

C3.56 Although radiation sterilization is a low-temperature process there ISnevertheless some increase in temperature above normal ambient temperaturesand this should be considered.

C3.57 There is no requirement for the packaging to be gas permeable. If thepackaging is gas tight it may reasonably be assumed to be a satisfactory barrierto microbial contamination.

C3.58 Many materials are structurally altered by the radiation process; theymay become hardened and embrittled, or discoloured, for example.

C3.59 These radiation induced changes may be beneficial or disadvantageousto the subsequent performance of the packaging or they may simply beaesthetically unacceptable, for example the yellowing which occurs with somePVC materials.

C3.60 Many polymers are now available specifically formulated withstabilisers which make them suitable for use in irradiation processes. Theadhesives used to seal packages must also be considered for potentially adverseeffects of the radiation.

C3.61 For most hospital users, with only small numbers of items to beirradiated, the advice of the sub-contractor providing the irradiation sterilizationservice should be sought. Based on their experience of radiation sterilization ofsimilar products they will often be able to suggest appropriate packaging whichcan be validated by comparison with previously validated products.

Compatibility with the labelling system

C3.62 The importance as labelling as an integral element of the productpackaging has been stressed (see paragraphs C1.15 and C2.19 to C2.30).

C3.63 Labelling may take a number of forms, including:

• labelling printed directly on the packaging;

• printed labels attached to the surface of the packaging by adhesive, etc.

C3.64 Whether labels are printed directly on the packaging or onto discretelabels which are subsequently attached to the pack, the labelling systemshould:

a. not adversely affect the compatibility of the packaging with thesterilization process to be used, for example by excessively restricting theporous area available for gas exchange;

b. not be rendered illegible by the sterilization process to be used;

c . not employ ink of a type which may

(i) transfer to the pack contents;

(ii) react with the packaging to impair its utility;

(iii) change colour and render the label Illegible;

(iv) interfere with the sterilization process by, for example, evolution ofvolatile components.

C3.65 Labels fixed to the surface of the packaging must be able to withstandexposure to the sterilization process and the defined storage and transportconditions without becoming detached.

C3.66 Given the low cost of computerised label printing systems there can belittle justification for using hand-written labels with the inevitable variation inlegibility that this causes.

C3.67 Writing on the packaging also presents an unacceptably high risk ofcausing damage to, for example, paper packaging, which may not be readilyvisible but is sufficient to breach the microbial barrier properties of the material.Furthermore, some pens, such as ‘felt-tip’ pens and ‘marker’ pens, have inkswhich may release volatile components in sufficient quantities to interfere withthe correct functioning of a steam sterilizer.

Compatibility with requirements for aseptic opening

C3.68 Failure to consider adequately how a pack is to be opened and thecontents removed may significantly increase the chance of contaminationoccurring. With inadequate provision for aseptic opening a 10-3 probability ofcontamination is easily possible which compares unfavourably with a 10-6

probability of sterility required as a minimum standard before labelling aproduct as sterile (EN 556).

C3.69 The means of sealing or closing the pack should be tamper evident inorder that the user may rely upon the integrity of the contents.

C3.70 For sterile products the other major consideration at the point of usemust be the ability to remove the product from the packaging without itbecoming contaminated with micro-organisms, in other words the asepticremoval of the product.

C3.71 The provision of aseptic removal may be influenced by a number ofelements in the design of the packaged product Including:

• the type of product;

• the packaging system chosen;

• the method of closure or sealing;

• the number of layers of packaging material;

• the arrangement of the contents of the pack;

• the use of special equipment to remove the contents.

C3.72 Sterile medicinal products include both parenteral and topicalpreparations. The former are predominantly aqueous solutions whereas thelatter may be aqueous solutions, oils, emulsions (ointments or creams), or drypowders.

C3.73 The packaging system employed for sterile medicinal products willnormally consist of a closed rigid or flexible container as the primary pack. Thismay be closed by being hermetically sealed or by being sealed with apenetrable (or removable) elastomeric closure (such as a bung, stopper or disk)held in place with a screwed cap or crimped overseal.

C3.74 Sterile medicinal products are usually best presented in single-use form.Where a multi-use presentation is employed there will be a requirement for asuitable preservative to be included in the product formulation.

C3.75 The primary pack may need to be overwrapped if it is necessary toprovide for aseptic handling of the primary pack.

C3.76 Sterile medical devices may be presented as single items such asindividual instruments, dressings, etc or, as a single pack containing multipleitems; the composition of which is designed so that contents comprise theitems required for one (or more) particular procedure(s).

C3.77 These are commonly described in a variety of terms such as:

• Basic packs (dressing packs which may or may not contain instruments);

• Composite packs (instruments, dressings and other equipment/utensils);

• Supplementary packs (which include instruments, utensils, dressings foruse with basic packs and composite packs);

• Procedure packs (which contain all the instruments, drapes, dressings andutensils required for a particular procedure);

• Linen packs packs (which contain all the drapes required for a particularprocedure);

• Gown packs, dressing packs, etc.

C3.78 The packaging system employed for sterile medical devices may consistof flexible or rigid packaging, or the two types used in combination; and maybe intended for single use, or be re-usable or a be combination of single useand re-usable.

C3.79 These may be closed by heat-seal, adhesive, compression gaskets, ortortuous path closures. A common format used in hospital SSDs is a packformed from a rigid tray wrapped in a flexible packaging material. The tray maybe re-usable metal or plastic, such as polypropylene, or single use, such asmetal foil, moulded pulp, folded cardboard.

C3.80 For medical devices the arrangement of the pack contents will be ofimportance. The contents generally are arranged so that when the pack isopened they are available in an order convenient to the user for the intendedpurpose and suitable for aseptic removal.

C3.81 The method of opening the sealed or closed pack and/or removing thecontents affects the aseptic removal capability. The various sealing and closingmethods may involve particular risks with regard to transfer of contaminationfrom the outside surface of the pack, or to transfer of fragments of thepackaging.

C3.82 Tortuous path seals formed by the folding of flexible packagingmaterial may be constructed so that they may be opened without touching theinner surfaces.

C3.83 Pealable seals are used on heat sealed, and some adhesive-sealed,flexible packs and on many commercially produced packs, for example liddedblister packs. The construction of the seal should allow the opposing surfacesto be grasped easily and the seal on separating should not cause fibre sheddingby, say, the splitting or tearing of either surface.

C3.84 Both flexible and rigid packaging systems are used which are intendedto be broken, cut or torn open, for example ampoules, paper bags andpouches. It is important that this can be done without introducingcontamination into the pack contents either from fragments of the packaging(for example glass particles from an ampoule), or from instruments used in theopening procedure, such as scissors for cutting open paper bags.

C3.85 Rigid re-usable containers for dry goods should have a tamper evidentseal which must be broken before the container can be unlatched and the lidopened.

C3.86 Both single-use and re-usable containers for liquids, particularly thoseintended for topical administration or laboratory use, may have a seal which isformed from a compressible gasket (for example a rubber wad or stopper) heldin place by, or as an integral part of, a screw capped lid. Aseptic removal of thecontents will depend not only on the ease with which the cap and gasket canbe removed but also on the method used subsequently to dispense thecontents, for example pipetting, pouring.

C3.87 Both single-use and re-usable containers for liquids, particularly thoseintended for parenteral administration, may have a seal which must bepunctured and penetrated by a suitable device to remove the contents, forexample using a hypodermic needle and syringe to remove the contents of avial.

C3.88 The potential risk of introduction of contamination from surface of sealshould be considered. The external surface of the seal may need protection(overseal) which can be removed immediately before use, or the instructions foruse may require pre-treatment of the seal surface, for example by swappingwith a 70% m/v aqueous solution of spore-free isopropanol.

C3.89 For re-usable systems the ability of the closure to re-seal after eachpenetration will be an important consideration in the maintenance of sterility.

C3.90 The seal for either single-use or re-usable systems must be of amaterial which will not be damaged by the penetrating needle to the extentthat fragments of the closure will contaminate the contents of the container.

C3.91 Sealed packs should always be carefully inspected for seal integrity, oradventitious contamination, before being opened and this requirement shouldbe drawn to the users’ attention both in the labelling of the pack and on anyinstructions for use or training programme which may be given.

Compatibility with the contents

Medical devices

C3.92 The suitability of the packaging for use with the particular medicaldevice should be established. This should include limiting values for physicalcharacteristics of both the medical device as well as the stresses which will beimposed during sterilization and subsequent transport and storage.

C3.93 Factors to be considered include, but are not limited to:

• the mass and configuration of the medical device to be packed;

• the presence of sharp edges or protrusions;

the need for mechanical and other protection;•

• interactions with the packaging materials.

C3.94 Consideration of product interaction should also include physicalcontamination with the packaging material. Small particles introduced into thebody during, for example, surgical procedures are widely reported to causeclinical problems including inducing adhesions, granulomata and foreign bodyreactions in tissues.

Medicinal products

C3.95 Factors to be considered include:

• interactions with the packaging materials, including adsorption,absorption and chemical reactions with components of the packagingmaterials, for a period not less than the specified storage life under thespecified storage conditions;

• adverse effects on the contents due to gas or water vapour permeability,such as permitting loss of water from a formulation, or permitting theingress of oxygen and subsequent oxidation of one or more componentsof the formulation.

C3.96 Materials used for packaging should be compatible with the containedproduct, For example packaging intended for use with parenteral fluids shouldnot shed particulate material to an extent which could compromise the qualityof the parenteral being administered.

Laboratory products

C3.97 Factors to be considered include all those notedsections for medical devices and medicinal products.

in the two previous

Toxicity

C3.98 Packaging materials and/or systems should not release material knownto be toxic in sufficient quantity to cause a health hazard either before, duringor after sterilization under the specified conditions of use.

C3.99 Evidence that the packaging material and/or system does not eithercontain material known to be toxic, or contain material which may react duringthe sterilization process to form a substance known to be toxic, in sufficientquantity to cause a health hazard is normally sufficient to meet thisrequirement.

C3.100 Manufacturers of packaging are aware of this requirement andshould be able to provide evidence that the formulation of the packaging hasbeen reviewed by a competent toxicologist and found to meet thisrequirement.

Biocompatibility

C3.101 The biocompatibility of the packaging should be assessed with regardto the intended use of the pack contents. If particular requirements for theproduct to be sterilized, for example freedom from particulate matter, cannotbe established from the material specification for the packaging underconsideration expert advice should be sought. In the first instance this adviceshould come from the manufacturer of the device, who has a legal obligationto specify any particular requirements for the safe sterilization of the product.

C3.102 Test methods for bio-compatibility are described in EN 30933-1; theyrequire the services of a specialist laboratory.

Preservation of sterility

C3.103 The packaging materials and/or systems assembled in the form inwhich it will be presented to the sterilizers, when assembled, stored,transported and used in accordance with the producer’s instruction, shouldpreserve the sterility of the contents from the time at which they are renderedsterile to the expiry date specified by the manufacturer and/or the point of use.

C3.104 Preservation of sterility is achieved by preventing the ingress of micro-organisms. Many factors affect the probability of such ingress occurring. Theseinclude, but are not limited to:

• the concentration of micro-organism in the environment;

• the size of particle on which the micro-organisms occur;

• environmental conditions of temperature, humidity and pressure;

• the rate of change of these environmental conditions;

• flow rates through the layers of packaging material;

• pore size and other filtration parameters of the packaging material.

C3.105 There is no universally applicable, single test method which can beused to establish the microbial barrier properties of a pack.

For particular types or sizes of pack there are tests which may be of value as anoverall monitor of microbial barrier properties.

C3.106 For most practical purposes it is necessary to infer satisfactorymicrobial barrier performance from a combination of tests designed to testattributes of the packaging which are related to microbial barrier properties, forexample to test the gas tightness of seals.

C3.107 The time for which any packaging system will maintain the sterility ofthe pack contents is event related not time related. It is therefore necessary todefine, and control, the conditions for both storage and transport, withinwhich the pack will maintain the sterility of the contents.

Storage and transport of sterile packs

C3.108 It is necessary to ensure that the packaging is able to provide theprotection necessary to maintain the performance characteristics of:

• the packaging during storage and transport under the specifiedconditions;

• the contents during storage and transport under the specified conditions.

C3.109 When handled according to instructions, the packaging shouldprotect the product from physical damage and maintain the sterility of themedical device up to the point of use.

Number of layers of packaging material

C3.110 Products may be packaged in a single layer of packaging material, orin multiple layers. Multiple layers of packaging may be used to reduce thelikelihood of contamination during storage and when the pack is opened.

C3.111 When two layers of packaging are used to facilitate aseptic removalof the contents:

• the outer wrap is sealed and acts as a barrier to microbial penetration tothe product from the environment,

• the inner wrap may, or may not, be sealed and may, or may not, beintended to be a barrier to environmental microbial contamination. It actsas a protective cover during removal of the product.

C3.112 When the inner wrap is a microbial barrier it may serve to provideadditional assurance of the maintenance of sterility.

C3.113 This inner wrap, having been maintained in a sterile state by thepresence of the outer wrap, may be handled by persons, wearing sterile glovesand about to undertake an aseptic procedure.

C3.114 Moulded plastic shields covering hypodermic needles, plastic end-capson intravenous administration sets are two examples of inner wraps found oncommercially sterilized products. They may also serve additional functionsunrelated to the sterile nature of the product, such as mechanical protection,protection of operators from hazards associated with the product etc.

C3.115 Double wrapping is essential for equipment that will be used in anaseptic environment such as an operating room or a protective Isolation unit.

C3.116 In particular instances, triple-wrapped product may be necessary topermit the adoption of procedures with a high level of assurance that there willbe no contamination, for example transfer of laboratory products into a sterility

test containment facility or transfer of equipment and components into anaseptic manufacturing environment.

C3.117 Single wrapping may be more economical and appropriate when theproduct, although sterile, will not be used in an aseptic environment and willnot be used parenterally or to penetrate tissue, for example Ryles tubes,oesophageal and suction tubes, urine bags, rectal examination sets etc.

C3.118 The various layers of packaging may be used to provide for differentfunctional requirements, for example many surgical instrument and dressingspacks are wrapped with an inner layer of paper or cloth which is used toprovide a sterile field when opened onto a table, trolley or tray at the point ofuse.

C3.119 Two or more layers of packaging may be used together to provide afunctional requirement which neither alone could meet, for example a singlelayer of textile may not be an adequate barrier to microbial penetration buttwo layers in combination may provide satisfactory performance.

Primary and secondary packaging

C3.120 If two layers used together are needed to meet a basic performancerequirement then layers both together constitute the primary pack.

Secondary packaging

C3.121 Several individual units, each wrapped in its own primary packaging,may be packed together in a “shelf pack” which may consist of a carton,plastic film wrap, film-wrapped carton or similar.

C3.122 For distribution, multiples of individual units or shelf packs may bepacked in transit containers.

C3.123 These may be intended as single-use, for example fibreboard cartonsor re-usable, for example plastic or aluminium boxes. Their primary function isto withstand the predictable risks arising during transport and distribution.

C3.124 Some or all of the secondary packaging may be applied beforesterilization, especially in commercial sterilization. When this is the case thepackaging, in its entirety as presented to the sterilization process, must meetthe requirements for sterilization compatibility.

C3.125 When re-usable transport containers are employed, a documentedand monitored procedure for maintaining them in a clean, hygienic conditionand a good state of repair is necessary.

C4.0 Packaging materials andsystems

C4.1 The following section summarises various packaging systems andmaterials that are available, including methods of effecting suitable seals orclosures, their suitability for use with sterilization processes which may beemployed by hospital users, and equipment necessary for their effective use.

C4.2 The summary is wide ranging and comprehensive, but not exhaustive.The absence of a particular system or material should not be taken as implyingthat it is unsatisfactory for use, nor should the inclusion of a particular systemor material been seen as an endorsement of its use.

C4.3 The choice of suitable packaging systems and matera number of factors .These include, but are not limited to:

ials will b ebased on

• compatibility with available sterilization processes and other factors (seeparagraph C3.5);

• particular requirements of the user;

• availability and cost of suitable automatic equipment for filling, sealing,labelling;

• availability and cost of suitable re-processing facilities for re-usablepackaging;

• availability and cost of suitable disposal methods for used single-usepackaging;

• standardisation of packaging systems within a single production unit.

C4.4 There is no one packaging system that is “correct” for all applications;and for any particular application there may be several systems available noneof which is perfect. It may then be necessary to prioritise the requirements tobe met by the packaging and select the system which most nearly meets theserequirements (Table C2). The two characteristics which are afforded the highestpriority most often are compatibility with the sterilization process andmaintenance of sterility in storage and distribution.

Sterilization compatibility

Steam sterilization

Wrapped goods and porous loads

C4.5 Goods are normally double wrapped; at least one of the layers willusually be a sheet of paper, paper bag or paper/plastic pouch.

C4.6 The inner lining may be chosen primarily for its absorbency in order toretain condensate in a position from which it will be successfully evaporatedduring the drying stage of the sterilization cycle.

Table C2 Selection of packaging materials by sterilization process

Sterilization Re-usableprocess packaging

Single-usepackaging

Steam sterilization

for wrapped goods Containers (valve or filter)and porous loads* Textiles (cotton and/or

synthetic)

PapersPlastic/paper pouchesCellulose/synthetic wrapsSpun-bonded polyolefinsup to 121°C

for instruments and Free-draining “instrumentutensils orientation” trays

for aqueous fluids Glass bottlesGlass vialsPlastic bottles

Ethylene oxide Containers (valve or filter)

Dry heat

Radiation

Polypropylene boxesOpen cell foam (forinstrument protection)

Metal (eg aluminium)canistersGlass containers

Glass bottlesGlass vials/ampoulesPlastic bottlesPlastic pouches

PapersPlastic/paper pouchesSpun-bonded polyolefins

(eg Tyvek)

Plastic/paper pouchesPapers

Metal foilsPlastic films

Treated paperPolyethylenePolypropyleneMetal foilsVarious laminatesCardboard

(PVC)

* The same packaging materials are also suitable for use with LTS disinfectors

Fluids in sealed containers

C4.7 Glass or plastic bottles, vials or ampoules are used for rigid containersand plastic pouches, usually a laminated construction to optimise theperformance characteristics, are suitable for flexible containers.

Dry heat

C4.8 Aluminium cans or tubes, glass tubes or jars, each of which may besealed with push on caps, screw caps or crimp-on foil caps, are suitable for dryheat sterilization. Crimp-on foil caps with a pre-printed colour change indicatorare also available.

C4.9 Items may be wrapped in heavy or light gauge metal foil or, for itemssuch as laboratory glassware the foil may be used simply to seal the open endof the product.

C4.10 Plastic bags of the sort sold for roasting meat in domestic ovens mayalso be suitable.

LTSF

C4.11 Packaging may consist of paper, used as plain or creped wraps, or inthe form of bags or, in combination with plastic film as pouches.

C4.12 Light cardboard boxes, or corrugated polypropylene boxes, adequatelyvented and overwrapped with paper or other material as a bacterial barrier arealso suitable. When particularly delicate instruments are to be processed theuse of an open cell foam for support and protection is acceptable.

C4.13 The quantity of packaging should be kept to the minimum possible.

Irradiation

C4.14 Polythene/polyester/nylon or metal foil may be used. The material maybe non-porous and gas impermeable which gives good microbial barrierproperties. Paper, spun-bonded polymers and non-wovens can also be used butlose the advantage of a process that can deal with impermeable packaging.

Ethylene oxide

C4.15 For ethylene oxide sterilization a high permeability to air, steam andethylene oxide is essential.

C4.16 Paper bags or plastic/paper pouches are usually found to be mostconvenient for small articles. Wrapping in sheets of plain or crepe paper, ortextiles, may be required for large procedure trays containing endoscopes orother thermolabile equipment.

C4.17 Moulded foam inserts may also be used to provide protection forsensitive equipment such as endoscopes.

C4.18 Polythene bags with gas exchange ports of Tyvek are also suitable.

Bacterial barrier properties

C4.19 The basic requirement is for a material which will not allow theproduct within the pack to be contaminated by the ingress of microbes in theenvironment from the time that it is removed from the sterilizer, duringtransport and storage up to the point of use.

C4.20 With a non-porous material, where gas flow through the material canonly occur through diffusion, the material itself will be an absolute barrier tomicrobial contamination. The microbial barrier properties of the pack will thendepend on the adequacy of the seal or closure. For example, an ampoule, ifcorrectly sealed by fusion, and having no cracks or other flaws, will be anabsolute barrier to microbial contamination.

C4.21 When a porous material is used the barrier to microbial penetrationwill not be absolute; there will be always a finite possibility of a micro-organismpenetrating the barrier and potentially contaminating the pack.

C4.22 The probability of a micro-organism penetrating the barrier will dependon many factors, including, but not limited to:

• the rate of air flow through the web, which may be influenced by therate and extent of environmental changes in pressure and temperature;

• the relative humidity, which can affect both the pore size and surfacecharge of natural fibrous materials (paper, linen etc);

• the type and number of micro-organisms in the environment;

• the form in which they are presented, for example as single organisms or,as they are more usually found, on relatively large particles such as skinsquames;

• the nature of the product, which mayorganisms can survive or multiply.

influence whether contaminating

C4.23 The effect of these various factors is not the same for all materials. Forexample some porous materials are better at excluding particles of a given sizeat very low flow rates while other materials perform best at higher flow rates.

C4.24 It is apparent that the storage conditions will also be a controllingfactor in the maintenance of sterility. Dirty, damp conditions can give rise tohigh microbial counts in the environment; large and rapid changes oftemperature, and changes of pressure (including the slamming shut, or violentopening, of doors) will lead to an exchange of air between the contaminatedair of the environment and the interior of the pack.

C4.25 The ability to maintain sterility is primarily “event related” rather than“time related”, although even under controlled conditions there is a greaterprobability of an adverse event having occurred after prolonged storage.

C4.26 The most sensitive time for contamination through porous wrappingmaterial is when steam sterilized product has been removed from the sterilizerand is cooling down. During this process air will be taken into the warm andhumid environment in the pack.

Materials used in packaging

C4.27 The materials of which the packaging is made will necessarily limit thesterilization processes with which it is compatible as well as affecting its abilityto meet other performance requirements.

C4.28 Performance requirements for packaging materials include:

• permeability to air, steam and gaseous sterilants, (although this does notapply to materials intended for use with aqueous fluids in sealedcontainers, dry-heat sterilization by hot air or sterilization by ionisingirradiation);

• resistance to penetration by micro-organisms from the surroundingenvironment;

• resistance to punctures, tears and other mechanical damage which wouldbreach the barrier to microbial penetration;

• freedom from loose fibres and particles;

• freedom from toxic ingredients and non-fast dyes;

• compatibility with the contents under the proposed sterilizing conditions;

• compatibilitydegraded by

with the sterilization process to be used, that is, notit.

Textiles

C4.29 Textile fabrics are used for packaging; traditionally these are wovencotton materials but may also be cotton/polyester blends.

C4.30 Specialist fabrics are also available which may are intended to be waterrepellent while at the same time being gas permeable. This may be achieved byseveral means, for example a particularly tight weave of polyester fibres, or alaminated construction with a middle lamella of a suitable polymer film. Careneeds to be exercised in using these fabrics that the flow rate of both air andsteam through the fabric is adequate for the sterilization process.

C4.31 Textiles are often used as a wrapping material for heavy packs,especially of theatre instruments, which are to be sterilized in a porous-loadsteam sterilizer.

C4.32 Textiles are stronger than paper, and stronger than many non-wovens,and will resist tearing and rupture.

C4.33 However, textiles are generally a less efficient bacterial barrier thansterilization grade wrapping paper and should always be used in two or morelayers. The second layer may be a textile wrap also or a suitable sterilizationgrade wrapping paper. Alternatively, a sterilization grade paper bag may beused to enclose the textile-wrapped pack.

C4.34 Textile wraps are re-usable.

Papers and non-wovens

C4.35 Both papers, which are made from cellulose fibres, and non-wovens,made from a combination of cellulosic and synthetic fibres, may be used. Bothtypes are suitable for porous-load steam sterilization and most gas processesbecause they are permeable to air, steam and other gases.

C4.36 The original papers used for steam sterilization wrappers were kraftpapers produced for general purposes. Purpose made papers with bettercontrolled porosity and microbial barrier properties, and with enhanced wetstrength and water repellency are now used. These are available as plain sheets,creped sheets which give better drape characteristics, as bags and incombination with a plastic film as pouches (or reel material from whichpouches can be made).

C4.37 Good drape and handle characteristics are also provided by crepepaper (BS 6254 1989).

C4.38 Plain papers may be used as wraps or preformed into bags or pouches.The bags and pouches may be plain sided or may be gussetted toaccommodate bulky items.

C4.39 Wet strength and water repellency are specifically improved over“normal” papers by the impregnation of the paper with high wet-strengthresins.

C4.40 The water content of the paper may be maintained at a relatively highlevel, thus improving the feel and drape of the paper and minimisingsuperheating due to exothermal rehydration, by the addition of humectantssuch as sorbitol.

C4.41 Over many years experience the various forms of paper packaging havebeen demonstrated to provide an effective microbial barrier.

C4.42 Non-wovens are generally less effective as a microbial barrier and mayneed to be used in, or as one of, two layers; they are however generally softerwith better handling and drape characteristics.

C4.43 British Standards exist for all the paper packaging materials and shouldbe used as the basis for purchasing specifications. (These standards will bereplaced in due course with European Standards currently in preparation; thedraft standards cover the same range of requirements as the existingstandards.)

C4.44 Non-woven materials, made from a combination of natural andsynthetic fibres are also widely used. These are often used where otherwise re-usable textiles would be used. They are generally of greater porosity than paperwraps and for this reason may not be as effective as a microbial barrier. Theyhave higher tear and puncture resistance and are softer with better drapequalities. They may also show extremely good water repellency.

Synthetic materials and laminates

C4.45 Polymeric materials, or plastics, may be used in the manufacture ofrigid, semi-rigid, or flexible packaging systems.

C4.46 They may be in the form of sheet or film, which is non-porous, or beproduced as a spun-bonded or non-woven sheet which is porous.

C4.47 Plastic materials are also used in the manufacture of mouldedcontainers, for dry products or for liquids.

C4.48 Film or sheet material may be an absolute barrier to microbes if it isfree from pinholes. Although it may be non-porous that does not necessarilymean that it will be impermeable. Most polymers have some permeability togas, air, and water vapour. The extent of the permeability varies withtemperature, concentration gradient of the diffusing substance etc andalthough generally low may be important, for example in the long term storageand stability of a pharmaceutical product.

C4.49 Plastic materials are generally robust and resistant to tearing. Theextent to which they show puncture resistance depends much more on thepolymer and film thickness used. There have been in the past major problemswith thin-film moulded polyethylene commercially produced packs beingbreached by the sharp edges of the product within.

C4.50 Plastic materials can usually be heat-sealed to give a high-integritybarrier.

Polyethylene (polythene)

C4.51 Polyethylene is effectively impermeable to air and water and is notsuitable therefore for general use in ethylene oxide sterilization processeswithout special precautions. However very thin films (up to 0.076 mm) thickallow the passage of ethylene oxide (by dissolving in the thin film and then

evaporating from the inner surface). Paper laminated with a thin polythene filmmay thus be used to provide a heat sealable paper for use in ethylene oxidesterilization.

C4.52 High-density polyethylene is produced as a spun-bonded, non-woven(known commercially as Tyvek) paper-like material. It is very tough, andalthough it is porous like paper it is water repellent.

C4.53 In commercial use it has been found to provide a satisfactory bacterialbarrier. It is frequently used in packs which are to be ethylene oxide sterilizedand may be used with a clear film in the form of a pouch, as venting panels inimpermeable bags made of, for example polythene, or as a sealing lid on blisterpacks.

C4.54 It has also been found suitable for use in steam sterilizers operating atsterilization temperatures up to 121°C.

C4.55 It has some disadvantages in that it may attract dust and fibres owingto its electrostatic character, it can be difficult to print on and also it may bedifficult to seal, although these latter difficulties largely can be overcome byusing non-oil based inks and lacquering with a suitable heat-seal lacquer,respectively. It is also expensive compared with paper.

C4.56 At temperatures above 125°C even high-density polythene hassoftened too much to be used on its own as an effective packaging materialand it is therefore unsuitable for steam sterilization at 126°C or 134°C of forhot-air sterilization.

C4.57 Polythene can be sterilized by ionising radiation.

Polyester

C4.58 Polyester, in the form known as oriented or crystallised polyester, isused as a laminate with polythene in the construction of paper/plastic pouchesand reel material.

C4.59 The polythene forms the inner surface which is heat sealed to thepaper. The outer layer of the plastic laminate is polyester which gives therequired mechanical strength at elevated temperature as well as a goodprinting surface.

Polyvinyl chloride (PVC)

C4.60 PVC generally has a very low stability to both heat and ionisingradiation.

C4.61 PVC will absorb ethylene oxide in large amounts. This is exacerbatedby the ethylene oxide combining with the phthalate plasticiser, from which it isaerated only very slowly under ambient conditions.

C4.62 Some grades of PVC are used for the moulded bases of commerciallyavailable blister packs.

Polypropylene and polycarbonate

C4.63 Both polypropylene and polycarbonate are relatively heat stablematerials.

C4.64 Polypropylene has a very low permeability to air, moisture and ethylene

oxide. It has been used extensively, either separately or in combination withother polymer laminates, as flexible, semi-rigid or rigid containers for heatsterilization of water and aqueous fluids.

C4.65 Polypropylene has been laminated with aluminium foil for use aspackaging for wet or oily materials such as skin swabs, alcohol wipes.

C4.66 Polycarbonate has been used extensivelyautoclavable laboratory bottles (at 121°C).

for th emanufact ure of

C4.67 Certain grades of polypropylene, specifically formulated for thepurpose, can be radiation sterilized.

Nylon

C4.68 Nylon is heat stable, and is also steam permeable but it is impermeableto air. Packaging constructed entirely from nylon film is unsuitable for steamsterilization because the air retained in the package may interfere with effectivesterilization. It may however be used effectively in combination with a porousmaterial, such as paper, to form a steam-sterilizable pouch.

Glass containers

C4.69 Glass containers, are usually in the form of ampoules, vials, jars orbottles and come in a variety of capacities and shapes, with several differentclosure systems.

C4.70 Three different grades of glass are available.

a. Soda glass is normally the cheapest (also referred to as Grade I). It issubject to hydrolytic attack particularly when autoclaved containingaqueous solutions. Solutions sterilized in bottles made of soda glass maybecome contaminated with reactive silicates and show an increased pH.Such bottles are rarely intended for more than a single use.

b. Sulphated soda glass, also referred to as Grade II, is soda glass which isprotected against hydrolytic attack by a surface coating of sulphate. Thecoating is normally applied by sublimation of ammonium sulphate ontothe surface of the hot glass concurrently with annealing during themanufacturing process. Bottles made of sulphated soda glass are rarelyintended for more than a single use and, if re-used, the sulphate coatingis eventually lost and the glass is once again subject to hydrolytic attack.

c. Borosilicate glass, also referred to as Grade III, is much more resistant tohydrolytic attack than Grade I or II glass and is generally the preferredmaterial for containers which are to be used for autoclaving aqueoussolutions. Providing there is a suitable cleaning process compatible withthe intended end-use, bottles made of borosilicate glass may be re-used anumber of times.

C4.71 Borosilicate glass also has better thermal shock resistancecharacteristics than soda glass when used in a similar container.

C4.72 Glass containers may also be used for dry heat sterilization, and canwithstand radiation sterilization. However, irradiation causes a darkening of theglass which may be aesthetically unacceptable.

Metals

C4.73 Metals are used in the fabrication of sterilization containers for use inboth steam and hot-air sterilization processes, and to a lesser extent in gasprocesses such as LTSF or ethylene oxide. Since the material is neither porousnor permeable it must be constructed with a suitable venting system for use insterilization processes other than dry heat or radiation.

C4.74 The choice of metal should be based on consideration of both itscorrosion resistance to the sterilization process, for example in a steamatmosphere, and on its thermal characteristics. The ideal material would have ahigh thermal conductivity and a low heat capacity and would attain therequired temperature quickly, uniformly and without the formation of excessiveamounts of condensate.

C4.75 In practice, the choice is usually between aluminium, anodised orotherwise surface treated to give it suitable corrosion resistance, and a suitablegrade of stainless steel.

Single-use packaging

C4.76 Both flexible andintended for single use.

rigid packaging systems are available which are

C4.77 The recently enacted medical device regulations (see Chapter C2)include a requirement that sterile medical devices be designed, manufacturedand packed in a non-reusable pack and/or according to appropriate proceduresto ensure that they are sterile when placed on the market. There is thus aclearly stated preference for single-use packaging as the primary packaging forsterile medical devices.

Paper or textile wraps

C4.78 For wrapping materials two different folding methods have beenadopted, both of which, when correctly executed, provide a suitable tortuouspath to prevent the ingress of contamination.

C4.79 For large packs the parcel fold is the preferred method (see Figure C1).

C4.80 The pack contents are placed on the wrap, approximately in the centreof the wrap. The long edge of the contents should be aligned parallel to thelong edge of the wrap.

C4.81 One of the long edges of the wrap is folded over the pack contents tooverlap the centre line, and the edge of the wrap is turned back on itself. Thefold made by the turning back of the wrap should overlap the centre line ofthe contents.

C4.82 The opposite side of the wrap is then folded over pack contents tooverlap the centre line (and the side already folded over the pack contents),and the edge is turned back on itself.

C4.83 The ends beyond the short side of the contents are then folded to apoint and each is then folded over the contents.

C4.84 The same procedure may then be repeated for an outer wrap(s).

C4.85 The wrap is secured in position using pressure-sensitive adhesive tape(high-temperature masking tape or autoclave indicator tape) or by tying withtape or cords.

C4.86 For smaller packs the envelope fold is preferred (see Figure C2).

C4.87 In the envelope fold method the contents are placed on the wrapdiagonally and slightly off the centre line.

C4.88 The section of the wrap with the shorter corner-to-pack length isfolded over the contents by bringing the corner to the centre.

C4.89 This is repeated with the corners to the right and left of the first foldedcorner.

C4.90 In each case the corner is turned back to provide a flap for opening.

C4.91 Finally the larger fold is brought over the top and tucked in under theearlier folds with a corner protruding, to facilitate aseptic opening.

C4.92 The envelope fold if properly executed is quite secure without furtherattention but if preferred may be secured also with tape or by tying.

Paper bags, paper/plastic pouches

Folding

C4.93 Folding is the simplest method to obtain a satisfactory closure for bothpouches and bags, although it may not be convenient for high volumeproduction (see Figure C3).

C4.94 The corners atto give mitred corners.

the open end of the bag or pouch are folded diagonally

C4.95 The top of the bag or pouch is then folded over three times insuccession and secured in place with a piece of high-temperature maskingtape, or autoclave indicator tape.

C4.96 The folded top should always be secured with tape; staples shouldnever be used because of the holes that are then made in the package.

C4.97 The folded top may be opened by cutting through the bag or pouchwith a pair of sterile scissors. For non-critical applications it may be torn open;it should not be opened by removing the tape and unfolding the closure.

Self-seal

C4.98 Self-seal bags and pouches are closed by folding as described for plaintop bags and pouches, above. However the bag or pouch is manufactured withan impact adhesive coating in a small area of the paper, which is protectedbefore use by a piece of “release paper”.

C4.99 When the bag has been filled the top is folded over as previouslydescribed, the release paper is removed and the adhesive patch is pressed ontothe surface of the bag to secure the folded top in place.

Heat seal

C4.100 Paper bags and paper/plasticin forms suitable for heat sealing.

pouches and reel material are available

C4.101 The melting point of the heat-seal will effectively limit the maximumtemperature at which the pack can be used. Heat-seal packaging should not beused at temperatures above those specified by the packaging manufacturer.

C4.102 Heat sealing is performed by compressing the opposing sides ofpackaging, coated on one or both inner surfaces with a lacquer, adhesive orpolymer film, between heated plates.

C4.103 Packaging intended for heat sealing may be film coated, gridlacquered, or have an adhesive band.

C4.104 Film-coated heat-seal packaging has a thin film of a suitable polymer,such as polythene, laminated to the inner surface. When heated this meltssufficiently to fuse with the opposing surface and form a seal. The heat-sealpolymer may be laminated to another plastic or to paper. The polymer film, ifapplied to the paper element, may limit the porosity of the pack.

C4.105 Grid-lacquered heat-seal packaging has one side, usually the paper,printed with a heat-seal adhesive in a repeating diamond pattern all over theinner surface. Care needs to be taken that the width of the heat-seal issufficient to ensure that there is a continuous seal across the width of thepackaging.

C4.106 Adhesive-coated heat-seal packaging has a band of heat-sealadhesive printed on the inner surface of the packaging in the area where theheat-seal is to be made. The adhesive is coloured, usually blue, to aididentification of the heat-seal area.

C4.107 The seals need to be peelable. They should peel without splitting,tearing or shedding paper fibres since fibres can cause adverse reactions ifintroduced into open wounds.

C4.108 Peelability is a compromise between seal strength and the peelcharacteristics required which can only be achieved by use of the correct heat-sealing conditions.

C4.109 The heat-seal may be a single line, in which case it should be not lessthan 5 mm deep and extend across the width of the pack, or a series of lineseach about 1 mm wide and 1 mm apart to give a seal width of about 9 mm,with each line extending across the full width of the pack.

C4.110 The heat-sealing process must be undertaken with care. Creases inthe packaging material can result in inadequate or uneven seals.

C4.111 A weak point in the heat-seal of paper bags may often be found inthe corners where the paper is folded back on itself and in gusseted packswhere four thicknesses of material become two. This latter problem can beminimised by reverse folding the gusset in the area to be heat sealed, beforesealing.

C4.112 The effect of the sterilization process on heat seals must beconsidered. The elevated temperatures involved in steam sterilization canweaken the seals. Ethylene oxide gas leaves many seals unaffected but cancause embrittlement of others.

C4.113 Heat sealing is not only used for flexible packaging. It may be usedalso on rigid packaging when lids are sealed onto moulded plastic bases. Thebase tray may be moulded in-line just before filling or may be pre-formed. The

lid may be of paper, Tyvek or other porous material for use in steam or gassterilization processes or of impermeable film for use with radiation sterilization.

Glass containers

C4.114 Bottles and vials are extensively used for aqueous solutions for use astopical and parenteral medicines, microbiology media, laboratory reagents, invitro diagnostics, disinfectants, etc which are to be sterilized by moist heat.

C4.115 Glass containers mayaqueous liquids, such as oils.

also be used for hot air sterilization of non-

C4.116 Containers should never be filled with a volume greater than themanufacturer’s recommended maximum.

Ampoules - fusion seal

C4.117 Two forms of glass ampoule are available; one form intended only forautomatic (or semi-automatic) filling and sealing and one which is suitable formanual sealing.

C4.118 Ampoules intended for automatic filling and sealing may be supplied,internally clean, sterile and apyrogenic, with the neck closed by a “bubble” ofglass. During the automatic filling process this “bubble” is melted by a flamedirected vertically downwards to open the ampoule immediately prior to filling.This normally takes place in an environment controlled to be free fromcontamination. This type of ampoule is not suitable for manual filling andsealing operations.

C4.119 The relevant DIN standards may be used as suitable specifications.

C4.120 Ampoules are sealed by fusion. After filling, the neck of the ampouleis heated, almost invariably in a gas flame, until the glass softens and the wallsof the neck coalesce, surplus unmelted glass in the neck above the point ofmelting is drawn away and the fused end of the neck is allowed to cool.

C4.121 For any given design of ampoule, the temperature of the flame, theduration of heating and the time and speed at which the surplus neck materialis drawn off all affect the quality of the seal. When correctly performed the sealis as strong, or stronger than other parts of the ampoule.

C4.122 Ampoules for use in freeze driers are similarly sealed by fusion.

C4.123 Ampoules are opened by breaking off the neck. This may befacilitated by the inclusion of a deliberate weak point, in the form of a breakring, at the base of the neck during manufacture. Other methods which areavailable include notching the neck of the ampoule with a glass file, creating afracture line by the application of a hot wire or rod and several commerciallyavailable devices.

C4.124 Whichever method is to be employed, users should be givenappropriate instructions and training and should always take precautions toprotect their hands from injury due to broken glass.

C4.125 Ampoules are produced to a high level of consistency and faults insealing are likely to be due to poor setting up or control of the sealing methodand rarely, if ever, due to variations in the ampoules.

C4.126 After the ampoules have cooled, careful visual examination,preferably using a magnifier and a polarised light source, should be used toinspect the seal and any showing cracks, thinning or “blowing” of the seal andsharp protrusions or “tails” of glass, should be rejected.

C4.127 A vertical drop of 10-15 cm, for example inside a tube of suitablediameter so that the sealed end impacts onto a solid surface, such as a plasticlaminate, may also be used to test the ampoule seal. A satisfactory seal willsurvive, whereas a weak seal will break.

Vials and bottles

C4.128 As manufactured, glass bottles are generally clean, sterile andapyrogenic. Nevertheless they should be washed before use since they mayhave become contaminated during packaging and distribution, unless specialprecautions were taken to avoid this happening.

Screw caps

C4.129 Screw caps may be made of metal or plastic. They may be used toused to retain in place a separate elastomeric seal, such as a stopper or a wad,or they may incorporate a seal within the cap. In either case the seal is formedby compression of a deformable sealing material between the cap and the glasscontainer. The compressive force applied is a key factor in creating a leak-tightseal.

C4.130 Metal caps may “back-off” during autoclaving. The differentialthermal expansion of the metal of the cap and the glass of the bottle combineto make the cap unscrew slightly during processing. This rarely happens withplastic screwcaps.

C4. 131 The problem can be minimised for metal caps by carefulthe extent to which the cap is tightened before sterilization.

control over

C4.132 Devices to control the force used to tighten the cap (torque) shouldbe used both to ensure reliable sealing and to minimise the risk ofovertightening which can damage the cap or make it difficult to remove

Crimp caps

C4.133 Crimp caps are metal, or sometimes plastic, capsules used to retainan elastomeric seal, usually in the form of a stopper, in position in the neck ofthe container.

C4.134 During the application of the crimp seal, pressure is applied tocompress the stopper slightly against the top surface of the neck finish of thebottle. The skirt of the overseal is bent under the base of the retaining rim onthe bottle neck by the crimping device. This retains the stopper in place andmaintains it under slight compression to provide a good seal.

C4.135 During steam sterilization of the sealed container the pressure appliedby the crimp may be released to some extent by the thermal expansion of themetal capsule. This, and the high internal pressure generated within thecontainer, may cause the seal to leak. It should not be assumed that a sealwhich is demonstrably leak tight at room temperature will remain sothroughout the various stages of steam sterilization.

Re-usable packaging

Textiles

C4.136 Textiles are used in combination with aluminium trays for packs oftheatre instruments.

C4.137 The textile wraps should be laundered before each re-use.

C4.138 Control should be exercised over the laundry process to ensure thatfabric softeners and fresheners are not used since many of these containvolatile components which will evolve gas during steam sterilization andcompromise the efficacy of the sterilization process.

C4.139 The importance of thorough inspection before re-use cannot be over-emphasised. A light table should be used, and wraps with pinholes, clearlyvisible as points of light, should not be used.

C4.140 The location of the defect should be clearly marked and the item sentfor repair by means of a heat-seal patch. Sewn patches are not acceptablebecause of the needle holes created around the patch.

C4.141 Worn textile wraps are readily discernible since the light will shinethrough the more open weave that occurs as the fabric wears. These should nolonger be used as a sterile packaging wrap.

Containers for solid goods

Impermeable or unvented containers

C4.142 Aluminium tubes with crimped foil caps and larger canisters (madefrom aluminium, copper or stainless steel) with slide or screw-fit caps may beused satisfactorily for hot-air sterilization. Containers of this sort are usedfrequently for pipettes or glassware in the laboratory.

Open-topped trays and perforated containers

C4.143 Trays for containing sets of theatre instruments, or similar, are oftenconstructed in aluminium. Plastics such as polypropylene may also be used. Thetrays may have solid bases and sides or be equipped with drainage ports toallow condensate formed during steam sterilization to run off.

C4.144 When condensate drainage is provided it is necessary to ensure thatthe condensate is not discharged onto other parts of the sterilizer load, whichwill then emerge form the sterilizer wet.

C4.145 Trays may be overwrapped in textiles, single-use wraps or bags, or acombination of these materials to achieve the required protection, absorbencyand microbial barrier properties.

Instrument orientation trays

C4.146 These trays, usually constructed in metal, are fitted with retainingclips designed to hold a particular set of instruments in position. They are oftenfound in dental practice and also for use with sets of orthopaedic instrumentsand rigid endoscopic instruments.

C4.147 They are almost invariably fully vented, or unlidded, and in thiscondition may be suitable for use in a steam sterilizer intended for unwrappedinstruments and utensils (see paragraph 3.23).

Dressings drums

C4.148 Perforated metal containers, fitted with a filter material and closablelouvres were specified in BS 3281, 1960, for use as “dressings drums”. Thesewere intended to contain dressings and porous goods sufficient for a numberof clinical procedures.The product has been regarded as obsolete except for itsuse, until recently, as a convenient container for towels for the Bowie and Dicktest. Even this use has now been discontinued.

C4.149 There is, however, a new generation of re-usable rigid containersintended for use as a packaging system in steam (and in some cases, gas)sterilization processes. These are intended to contain instruments and/or porousgoods which will be used in a single clinical procedure. They are thus more akinto the trays described in paragraphs C4.143 to C4.145 than to the obsoletedressings drums.

Re-usable rigid containers

C4.150 A European standard specifying performance requirements for rigidre-usable containers is in preparation. When adopted it will be published as BSEN 868 – 8.

C4.151 Container systems are constructed in a variety of materials and thosefrom various manufacturers differ greatly in design, construction and mode ofoperation.

C4.152 The containers are constructed from impermeable materials. The jointbetween the lid and the base is sealed by means of a suitable gasket, whichshould be accessible for inspection and cleaning between uses.

C4.153 In order to permit the flow of gases (air and steam and, whereapplicable, sterilant gas) in and out of the container that is required by thesterilization process the containers are fitted with one or more sterilant ports.

C4.154 Two different operating principles are used for the sterilant ports,although both may be used in combination. The exchange of gases may bethrough a porous filter material or through a valve system.

C4.155 The filter system is little different in principle from the porouspackaging systems considered previously. Its compatibility with the sterilizationprocess depends on its porosity and on being able to provide the necessaryflow rate through the filter to permit attainment of the sterilizing conditionswithin the container.

C4.156 The ability to maintain sterility depends on the filter efficacy andwhether it is able to exclude particles of a size which may contain viableorganisms. The small area of surface available compared with the volume ofthe pack produces relatively high flow rates across the filter material and thisinfluences the materials which can be used effectively.

C4.157 If a re-usable filter is used then great care is needed to ensure that:

• it has not become partially blocked, thus impairing the flow of gases andcompromising the sterilization process;

• it has not been damaged, thus allowing the passage of unfiltered gaseswhich would compromise the maintenance of sterility.

C4.158 Both re-usable and single-use filters need to be installed correctly sothat the filter is effectively sealed in the holder and there is no passage ofunfiltered gases around the filter.

C4.159 The alternative system for sterilant ports is the valve system.

C4.160 Outside the sterilizer the valve is normally closed and, if the seals onthe valves are effective, presents an impermeable barrier to externalcontamination.

C4.161 The valve system has to be arranged to open automatically in thesterilizer to permit the exchange of gases between the container and theenvironment.

C4.162 A number of systems are used by the various manufacturers but mostdepend on valves which open in response to a pressure difference between thecontainer and its surroundings. A diagram of the operation of such a system isshown in Figure C4.

C4.163 It is apparent that a finite pressure difference must exist across thevalve before it will open. The magnitude of the pressure difference will dependon the force exerted by the springs keeping the valve closed.

C4.164 If the pressure difference required to open the valve is too great, thecontents of the container will not be exposed to the sterilizing conditions in thesterilizer chamber. The correct functioning of the container is closely related tothe pressure change characteristics of the sterilization cycle.

C4.165 If the required pressure difference is too small the valve will openoutside the sterilizer due to changes in ambient pressure and temperature, thusallowing the inflow of unfiltered air from the environment.

C4.166 Some container systems are also fitted with a valve in the base of thecontainer which is used to allow condensate to drain away, to assist in dryingthe contents of the container.

C4.167 The condensate drain valve may be fitted with a thermostatic deviceto open the valve when it is above a specified temperature, say 80°C, or it mayoperate on pressure differential as previously described for valved sterilantports.

C4.168 After repeated use, the springs controlling a valved system will ageand the force exerted by them will change. It is essential that themanufacturer’s instructions for maintenance, testing and replacement of keycomponents such as seals, sterilant ports and drainage valves are followedrigorously.

C4.169 The performance of either type of container may be seriously affectedboth by the nature of the sterilization cycle (particularly the characteristics ofthe air removal phase and the drying stage) and by variations in the quality ofservices supplied to the sterilizer (for example the dryness fraction of thesteam). These variables are sterilizer and site specific respectively.

C4.170 It is necessary, therefore, to establish, by appropriate on-site testing,that any particular design which it is intended to use functions correctly in thespecific sterilization cycle with which it is to be processed, in the sterilizerswhich will be used in practice.

C4.171 Re-usable containers have a number of apparent advantages. Theyoffer excellent mechanical protection to the contents and a convenient,modular system for storage and distribution.

C4.172 The use of a solid-walled container gives the impression of providinggood protection against microbial and other environmental contamination. Inpractice the barrier properties are dependent on the adequacy of gaskets andseals and the sterilant ports described above.

C4.173 The condition and function of filters, valves, sealing gaskets andlocking systems needs to be verified on each container before each use.

C4.174 Between uses containers should be disassembled and cleanedfollowing the manufacturer’s recommendations. These usually suggest cleaningby washing with a mild detergent, either manually or in a washer/disinfector.

C4.175 The choice of detergent should accord strictly with the manufacturersrecommendations since a number of cleaning agents in common use can causecorrosion or surface cracking on the metal or plastic surface of containers.

C4.176 These containers are often used to return used and soiledinstruments, which are potentially contaminated. Whenever practicable theyshould be decontaminated and cleaned in a washer/disinfector.

C4.177 Most containers are fitted with interior baskets or mesh trays used tohold the instruments. These may be suitable to contain returned instruments asthey are processed through a washer disinfector.

C4.178 In use the containers need to be properly loaded if they are to beused successfully. The manufacturers recommendations concerning themaximum weight, the proportion or density of metal ware or rubber goods andthe presence and location of absorptive materials in the load should befollowed.

C4.179 Some containers are intended to be used in conjunction with porouspackaging materials, either as an inner or outer layer of packaging, whereasothers are intended to be used, and will only function correctly, without anyother packaging being present during sterilization. It is important that themanufacturer’s instructions are followed.

C4.180 Containers which are not intended for use with a second layer ofpackaging, that is those which can only function as a single packaging layer,are not suitable for use in an aseptic environment (see paragraphs C3.109ff).

C4.181 Containers manufactured to the proposed European Standard will besized in relation to the standard loading module for large steam sterilizers (seeEN 285). High packing densities within the sterilizer chamber can be achievedand it is important to ensure that the maximum permitted load for the sterilizeris not exceeded.

C4.182 To avoid problems with moisture retention within the container it maybe necessary to increase the time allowed for the drying stage of thesterilization cycle.

C4.183 Each container should be fitted with a tamper evident closure systemwhich should provide a clear indication when the integrity of the closure hasbeen compromised.

C4.184 The containers are designed to stack for storage purposes. Containersfrom any one manufacturer should stack securely but containers of differentprovenance may not.

C4.185 When purchasing this type of packaging system all the containersshould be from the same manufacturer to ensure compatibility.

C4.186 Re-usable containers are often promoted on the basis that they aremore cost effective than single-use packaging. A decision based on costgrounds requires careful evaluation of the initial capital cost, cleaning andmaintenance costs (including all equipment, components, consumables andlabour required), the working life (the number of re-uses) which themanufacturer is prepared to guarantee, the likelihood of damage or loss andthe cost of eventual disposal.

Glass containers

C4.187 Bottles intended for single use should not be re-used. Bottlesintended for multiple use are available for most applications.

C4.188 Re-usable containers should not be used for solutions intended forparenteral administration.

C4.189 The information given for single-use screw cap and crimp-on closuresis equally applicable to re-usable containers, with the following additionalrequirements.

Vials and bottles

Cleaning

C4.190 Before bottles can be satisfactorily re-used a cleaning procedure isrequired which has a demonstrated capability to remove any dirt orcontamination, as well as any residues from the previous use. It is alsoimportant that the cleaning process is well controlled and ensures that thereare no residues of cleaning agents.

C4.191 Cross-contamination can be most easily controlled by ensuring thatwhenever possible re-usable containers are only refilled with the same product,for example by reserving a set of bottles only for sterile water and another setonly for sterile isotonic saline and so on.

Inspection

C4.192 Inspection of the bottles after cleaning and prior to re-use shouldinclude a careful visual examination of the neck finish. A chipped or crackedneck finish could prevent an adequate seal or lead to the failure of the sealduring transport or storage. Bottles that have been damaged in this way shouldbe scrapped.

C4.193 Inspection of the outer surface of the bottle should also be made.Bottles being sterilized are subjected to considerable stress both from the highinternal pressures generated and from thermal shock. Scratches or othermechanical damage on the outer surface of the bottle weaken it andsignificantly reduce the pressure and the thermal shock which can be toleratedwithout breakage.

C4.194 One bottle breaking in a sterilizer load may provide sufficient force tocause others to break also. Re-usable bottles with surface damage should berejected and either used for applications which do not require steamsterilization or be scrapped.

C4.195 The inspection of the neck finish should also consider any damage tothe screw threads or the retaining shoulder on the outside of the neck ofbottles which are closed with screw caps or crimped seals respectively.

Screw caps

C4.196 Screw caps, and the elastomer wads, stoppers or bungs used inconjunction with them, are often regarded as re-usable, and many of them maybe satisfactorily re-used a number of times.

C4.197 The screw cap should be separated from any sealing wad andshould be thoroughly cleaned and inspected for damage before re-use.

both

C4.198 Metal caps that have been dented,wear on the threads, should be scrapped.

or are showing visible signs of

C4.199 Rubber wads and rubber stoppers should also be carefully inspectedfor surface damage and any showing cuts, abrasions, staining or permanentdeformation should be scrapped.

C4.200 Plastic screw caps with a built-in seal are also commonly used. Theseshould be inspected very carefully for damage to the thin sealing gasket whichis moulded into the inner surface of the cap. Any damage to this area willalmost certainly cause the cap to leak.

Crimp caps

C4.201 Crimp caps are not themselves re-usable but the bottles on whichthey may be used can be. A special tool and some care is needed to removecrimped seals without risk of injury.

C4.202 The old seal should be discarded. The seals are usually fabricatedfrom aluminium and the metal can therefore be reclaimed.

C4.203 The elastomer seal should also be scrapped.

C5.0 Purchase, quality control andstorage

C5.1 The purchase, handling and control of packaging materials should begiven similar attention to that given to components and other materialsincorporated directly into the product.

Purchase

C5.2 All packaging materials should be purchased, whenever possible, to aBritish Standard or other suitable specification from approved suppliers.

C5.3 Packaging material should be purchased only to an agreed, writtenspecification. When it is intended to purchase a catalogue item, thespecification for that item should be obtained from the supplier and used asthe basis of that purchase, and all subsequent purchases of the material. Thisshould ensure that the user is informed of any changes in specificationsubsequently made by the supplier.

C5.4 The purchase order should be based on not more than the quantitywhich can reasonably, be expected to be used within the manufacturer’s statedshelf life for the product.

C5.5 Although paper products, and other packaging materials, have aprolonged shelf life the manufacturer’s expiry date may relate to otherproperties of the product such as a process indicator or an heat-seal adhesivewhose performance may deteriorate on storage.

C5.6 The specification and purchase order should require that the material bedelivered in unopened containers, using covered vehicles, suitably protectedfrom water damage or soiling and that it is handled with care to preventmechanical damage.

C5.7 The packaging materials should be supplied suitably wrapped to providethe required protection when it is stored under the specified conditions.

Specification

C5.8 For medical devices and medicinal products,products also, the specification should include:

and generally for laboratory

• a description of the materials including:

- the designated name and any code or reference;

- the size;

- the quantity in each unit pack delivered;

- the reference, if any, to a pharmacopoeia1 monograph, British Standardor other published specification;

- the approved suppliers, and if possible, the original producer of thematerial;

- a specimen of printed materials;

• directions for sampling and testing, or reference to written procedures;

• qualitative and quantitative requirements with acceptance limits;

• storage conditions and precautions including the maximum period ofstorage.

Quality control

C5.9 In many cases users of packaging materials will lack the facilitiesnecessary to carry out a comprehensive independent assessment of deliveredmaterials for conformity to their purchase specification.

C5.10 Nevertheless every reasonable step should be taken to establishconformity. This requires that each delivery should be examined to ensure that:

• there is no visible damage to the shipment;

• the delivery note, the label description and the purchase order are inagreement concerning the quality, size and number of the material;

• that each consignment has clearly identifiable lot numbers;

• that each lot delivered is accompanied by a Certificate of Analysis orCertificate of Conformity, or if the delivery is a further supply from a lotpreviously received that the appropriate certificate is on record.

C5.11 When, due to the nature of the packaging or the product, it isnecessary to carry out tests, other than a careful visual appraisal, on incomingpackaging materials a random sample should be taken and submitted foranalysis.

C5.12 There should be a formal sampling plan which should take account of:

• the quantity received;

• the quality required;

• the nature of the material, and the risk involved if the material is not tospecification, for example if the product makes contact with thepackaging material;

• the established reliability of the packaging manufacturer.

C5.13 The number of samples taken should be specified statistically, inaccordance with a recognised standard, such as BS 6000 or BS 6001.

C5.14 In confirming that the material supplied is identical in every respectwith the material ordered particular attention should be paid to printed labelsand packaging materials.

C5.15 A system for segregating delivery of packaging materials which havenot been examined from those which have been found suitable for use shouldbe implemented.

C5.16 Provision should be made for the temporary secure storage, prior todisposal or return to the supplier, of material which was delivered but, onexamination was found not to conform to the specified requirements.

Storage

C5.17 Packaging materials should be stored under conditions which aremaintained within those specified by the manufacturer of the packaging. This isbest achieved by environmental control of the storage area.

C5.18 The temperature, and where necessary the humidity, of the storageenvironment should be monitored with a maximum-minimum thermometerand hygrometer, even if the store is not environmentally controlled.

C5.19 Paper and other moisture sensitive packaging materials should not bestored adjacent to:

• external walls or other surfaces which may be at a lower temperaturethan the ambient temperature of the store;

• sources of heat which could cause dehydration of the packagingmaterial.

C5.20 Sheet materials should be stored flat, not on edge.

C5.21 Packaging materials should be stored on shelves, clear of the floor.

C5.22 Pre-printed labels and other printed packaging materials should bestored in secure conditions which exclude unauthorised access and should betransported in separate containers in order to avoid mix-ups.

C5.23 Packaging materials should be issued for use only by authorisedpersonnel following an approved and documented procedure.

C5.24 Outdated or obsolete packaging material, especially printed material,should be destroyed and this disposal recorded.

C6.0 Validation of packagingsystems

C6.1 All materials and procedures for packaging should be specified indocumented form.

C6.2 Before a particular packaging system is adopted for a product, or groupof similar products, it should be evaluated to establish its suitability.

C6.3 This evaluation should be documented.

C6.4 Specific testing may not be necessary when appropriate data areavailable, historically from similar use (whether by the same or different sterileproduct manufacturers), from the manufacturers of the packaging system orfrom an independent third party.

C6.5 The factors that need to be consideredminimum, those listed in paragraph C3.5.

for evaluation include, as a

C6.6 The compatibility of the packaging with the sterilization process can beestablished for many packaging systems by demonstrating conformity of thepackaging and the sterilization process with published standards, for examplesterilization-grade paper bags manufactured in conformity to BS 6257 for usein a sterilizer conforming to BS 3970 Part 3 and operated in accordance withthe guidance given in this HTM may be presumed to be compatible.

C6.7 Re-usable containers should be subjected to thermometric performancetests before they are adopted as a packaging system. This may be accomplishedusing a container modified to provide a gas-tight thermocouple entry port andcarrying out tests essentially similar to the small load and full load testsdescribed in HTM 2010 Part 3 paragraphs 13.7 to 13.14 and 13.15 to 13.24respectively.

C6.8 The tests should be carried out with a container fully loaded with itemsof the type which it is intended to process. If both instruments and textiles areto be processed the container should be tested under both fully loadedconditions. The full load test should be carried out with the sterilizer fullyloaded with fully loaded containers.

C6.9 The temperature profile obtained should not show any delay in thecontents of the container equilibrating with the sterilization temperature in thechamber, when compared to the results obtained using a small-load test pack.

C6.10 Load dryness should be verified using either the hospital load testdescribed in HTM 2010 Part 3 paragraph 13.37 or, when quantitative resultsare necessary, by a modification of the method described in HTM 2010 Part 3paragraphs 13.25 to 13.36.

C6.11 The compatibility of the packaging with the labelling system willusually be established by using the labelled pack for such tests as may benecessary.

C6.12 The compatibility of the packaging with the user’s requirements at thepoint of use, for example aseptic opening, should be verified by consultationwith the user. Testing is rarely required.

C6.13 The sensitivity of the pack contents to particular risks, such asirradiation, moisture, mechanical shock, static discharge and the compatibilityof the packaging with the contents, for example the medical device ormedicinal substance, in other words, that the packaging has no adverse effecton the medical device or vice versa, will usually be apparent from historicaldata. When new products are to be packaged and sterilized, the instructionswhich the device manufacturer is required to provide should be followed.

C6.14 The protection provided by the packaging against adverseenvironmental influences which may reasonably be anticipated, such asmechanical shock, vibration, chemical or microbial contamination, may beconsidered in two stages:

a. First, the extent to which the environment to be encountered duringtransport and storage may be controlled. Secondly, the protectionprovided by the packaging.

b. Adequate performance of the packaging should be demonstrated underthe anticipated conditions of use by simulating the abuses a pack mayencounter during routine methods of transit and storage.

C6.15 Guidance on the methods to be adopted is given in BS 6082: ‘Guideto compilation of performance test schedule for complete, filled transportpackages’ Part 1 ‘General principles’ and BS 4826: ‘Testing of complete filledtransport packages’ Parts 1-14.

C6.16 The protection provided by the packaging against microbialcontamination should also be evaluated.

C6.17 Tests for bacterial penetration of packaging are beyond the experienceand competence of most hospital users and could only be carried out byspecialist subcontractors. There is no agreement on suitable test methods, orperformance standards, for the microbial barrier properties of sterile packs.

C6.18 The microbial barrier properties of a sterile pack are dependent onboth the materials of which the packaging is made and the construction of thepackage.

C6.19 Materials that are impermeable to gases may reasonably be assumedto present an absolute barrier to microbial contamination. When such materialsare used in the construction of a pack which is hermetically sealed (for exampleglass ampoules) the barrier may also be assumed to be absolute.

C6.20 Package testing may be avoided by the compilation of evidence thatthe materials of construction are themselves an adequate barrier together withevidence that all seals and closures are adequate barriers.

C6.21 Two different approaches have been adopted to testing porousmaterials for their ability to exclude microbial contamination; tests based onphysical particulate retention (for example the methylene blue test specified inBritish Standards for sterilization packaging) and tests based on the use ofmicro-organisms (for example the tests specified in German standards forsterilization packaging).

C6.22 For many materials a standard specification has been adopted whichspecifies the physical and/or chemical characteristics of the material which have

been shown to provide satisfactory performance against a standard penetrationtest. Whenever possible materials in compliance with one of these standardsshould be adopted so that purchases are to an agreed specification which willgive the required level of assurance.

C6.23 The methods available for verification of the adequacy of the seal orclosure depend on the method chosen. Seals formed in impermeable packagingmaterials can be tested by one of several leak test methods but these are notgenerally applicable to seals formed in porous materials, nor to closures whichrely upon a tortuous path to exclude microbial contamination.

C6.24 Heat seals are also dependent for their success on the performance ofthe heat sealer used. Several methods for testing heat seals are available butvisual examination of the quality and uniformity of the seal from samples ofpackaging taken before and after sterilization and before and after storage andJourney trials may be sufficient.

C6.25 Closures which rely on a tortuous path formed by folding are verydependent for their success on the skill of the operator forming the closure.There is good published evidence, from a number of studies carried out overmany years, that the closures described in paragraphs C4.78 to C4.97 aresatisfactory.

C6.26 For packaging materials to be used in gas or irradiation sterilizationprocesses it may be necessary to determine the extent and nature of microbialcontamination on the packaging before sterilization. This should not benecessary for steam sterilization processes operating at 134°C for not less thanthree minutes.

C6.27 When knowledge of the packaging bioburden is required thisinformation should be sought from the packaging manufacturer or it should bedetermined in accordance with EN 11174 by an appropriately experiencedlaboratory.

C6.28 When re-usable packaging systems are being evaluated it is importantthat the cleaning, inspection and maintenance procedures and methods arealso evaluated for their ability to consistently restore the packaging system tothe required condition for re-use.

C6.29 Before any performance testing is undertaken a test protocol should beprepared. This should document:

• the tests to be performed, including full details of the equipment andmethods to be used, personnel etc.;

• the purpose of the tests;

• the sequence in which the tests are to be carried out;

• the format in which the results are to be documented;

• the pass fail criteria for each attribute being evaluated.

C6.30 The test protocol and theof the validation documentation.

written report of the results should form part

C7.0 Facilities and environmentalcontrol for packagingoperations

Packaging operations

C7.1 In SSDs the assembly of components, placing them in primarypackaging and sealing or closing the packaging usually is referred to as a“packaging operation”. Thus is in contrast to pharmaceutical and laboratorypractice where the same operation is described usually as a “filling operation”and the term “packaging operation” is reserved for the subsequent, oftenpost-sterilization, application of secondary packaging. In the following section“packaging operation” refers to the application of primary packaging and anysecondary packaging which is included in the sterilization process.

C7.2 Detailed guidance on suitable facilities is given in Health Building Note13 - ‘Sterile services department’ HMSO 1992 and Health Building Note 29 -‘Accommodation for pharmaceutical services’ HMSO 1988.

General requirements

C7.3 All areas used for the reception, inspection, storage, filling, and sealingof packaging require a high standard of finish and cleanliness.

C7.4 Areas where clean, unpacked product is to be handled for, say, assemblyand packaging, need a controlled environment to minimise the potential forrecontamination of product by, for example mechanical ventilation or gowningprocedures.

C7.5 All exposed surfaces should be smooth, water resistant and sufficientlydurable to withstand frequent cleaning. The construction and any fitmentsshould be designed to be free from crevices and sharp internal corners, whichcan trap dirt.

C7.6 Areas where product, ready for incorporation into primary packaging,and primary packaging materials are exposed to the environment for significantperiods should be controlled to defined standards of environmental cleanliness.

C7.7 For SSDs there should be a dedicated room where the production ofpacks, trays etc takes place. This should be a controlled environment. HBN 13recommends that packaging facilities for SSDs should be controlled to BS 5295Class L and a detailed summary of the environmental needs of the various areasis provided in HBN 13, Appendix 5.

C7.8 The GMP Guide for Pharmaceuticals recommends that parenteralsolutions should be filled under a laminar flow work station (Grade A) within acleanroom controlled to Grade C.

C7.9 The provision of controlled, clean environments has additionalimplications for staff hygiene, gowning and entry procedures and the behaviourof personnel within the facility. These requirements are fully described in therelevant GMP guides.

C7.10 Doorways throughout the facility should be wide enough, and freefrom damaged or rough edges, to eliminate the danger of packs of product ontrolleys being damaged as they are wheeled through.

Facilities for packaging operations

Cleaning

C7.11 All operational areas of a sterile-product manufacturing facility need tobe maintained to a high standard of cleanliness.

C7.12 Detailed cleaning procedures and schedules should be documentedand their implementation monitored.

C7.13 For guidance on suitable procedures and schedules see ISSM Guide toGood Manufacturing Practice for NHS Sterile Services Departments and TheDoH MRS Guide to Water and Environmental Cleaning.

C7.14 Surface finishes and cleaning methods must be compatible. Appendix6 of HBN 13 suggests appropriate finishes.

C7.15 Cleaning equipment and facilities for the storage and preparation ofcleaning materials and equipment should be provided separately for areasbetween which cross-contamination could be problematic.

Cleaners’ room

C7.16 HBN 13 recommends the provision of a dedicated cleaning facility forthe packing room, and a separate, dedicated, cleaning facility for the linenpreparation area (if one is used).

C7.17 The cleaning facility provides storage for cleaning equipment andmaterials, a sink or sluice with hot and cold water of the appropriate qualityand other facilities needed for the cleaning and preparation of the cleaningequipment. In addition, it usually accommodates consumable items foroperational areas which are normally replaced by the cleaner. This wouldinclude plastic waste bags, liquid or leaf soap refills for dispensers in changingrooms etc.

C7.18 Hand washingcleaning facility.

and drying facilities should also be available in the

C7.19 Whether or not separate facilities are provided, it is necessary to ensurethat separate cleaning equipment is used for the assembly/packing area andother areas within the unit.

Sterile services departments - SSD

C7.20 The packing room receives single-use materials from materials’storeand reusable goods after the completion of appropriate decontaminationprocedures.

C7.21 The decontaminated re-usable goods will include components to beincorporated into packs and may include re-usable packaging, such as textiles,instrument trays, re-usable containers.

C7.22 Within each of the areas supplying the packing room, or at theinterface between these areas and the packing room there is usually provisionof inspection/verification facilities to ensure that all product transferred into thepacking room is the correct item and in a suitable condition for use.

C7.23 In the packing room these goods are then assembled into thecombinations specified to form the pre-set trays and procedure packs which arerequired. These are then packed in preparation for sterilization (see HBN 13paragraph 2.44).

Linen room

C7.24 Cleaning facility - dedicated required same as packing room. Textilesfor incorporation into packs may be product items, such as surgical drapes,towels or gowns, or they may be wrapping materials.

C7.25 Textiles for wrapping purposes may be received in the SSD aslaundered linen which has already been checked and folded to an agreedpattern or in bulk form, unchecked and unfolded.

C7.26 The SSD has an obligation to ensure that the laundry process is definedand controlled and the quality checks on the textiles to be used are rigorouslyapplied to ensure that the pre-determined standard is maintained, even if thelaundry has the devolved responsibility for inspecting the packaging textiles (seeparagraphs C4.136 to C4.141).

C7.27 When unchecked linen IS provided from the laundry, the SSD willrequire suitable inspection facilities within a linen preparation room.

C7.28 When textiles are to be used as the primary wrap for sterile packs theyhave to be inspected to a defined standard, which should include freedomfrom all tears, cuts and visible holes. A light table is essential for inspection tothis standard.

C7.29 When the textiles are used only as an inner wrap and it is Intendedthat the necessary bacterial barrier properties will be provided by an outer wrapof another material, such as a sterilization grade paper wrap or bag, a lessrigorous inspection standard may be accepted for the textiles. A large flatsurface where the wrap can be fully unfolded and a good standard of ambientlighting are still necessary.

C7.30 The linting of fabrics can be a major problem. Lint is a respiratoryhazard and a fire or explosion hazard and together with other dust maycontribute to an insanitary environment by providing a vehicle for the transferof micro-organisms.

Packing room

C7.31 The activities undertaken in the packing area may be summarised as to:

• receive QC released single use, re-usable and consumable items. Notethat in some units the QC Inspection on cleaned and decontaminateditems is carried out within the packing area. When this system is used,and particularly when inspection is done at the same time as assembly,great care is needed to ensure proper segregation of rejected items;

• assemble items into pre-set trays and procedure packs;

• verify that the contents match the specification;

• pack;

• close and/or seal the packaging system;

• label;

• verify the accuracy of the label;

• transfer to sterilizer.

C7.32 The packing room should be mechanically ventilated to ensure that theparticulate count and pressure differentials meet the requirements of BS 5295Class L in the “unmanned condition”.

C7.33 Although it may be possible to demonstrate that areas lackingmechanical ventilation can meet the required particulate standard when tested,this is not a satisfactory substitute. Mechanical ventilation is required to ensurethat the particulate standard can be met consistently and also to ensure thatthere is a positive pressure relative to surrounding areas to minimise the ingressof contamination.

C7.34 HBN 13 recommends that the air supply filters should have a minimumresistance of 85% when tested in accordance with BS 6540 Part 1 (EU6).

C7.35 Humidification may also be required to avoid dehydration andsubsequent problems.

C7.36 When plastic materials are being used for packaging excessively dryatmospheres can promote a build up of static electricity which causes problems,such as attraction of particulate material.

C7.37 Dry atmospheres may lead also to excessively dry absorbent materials,such as paper or cotton textiles. When steam sterilized the exothermalrehydration of these materials can lead to local superheating and impairment ofthe sterilization process.

C7.38 Ethylene oxide sterilization requires goods to be sterilized which havebeen humidified to provide an optimum moisture content. This can be greatlyfacilitated by the maintenance of appropriate ambient humidity duringassembly and packaging.

C7.39 The layout of the packing room should allow an orderly flow of workand should provide sufficient separation between activities to preclude thepossibility of mix-ups, mis-labelling etc.

C7.40 Work surfaces should be of sufficient size to allow the largestwrapping materials which will be used to be fully opened without draping overthe edges of the work surface.

C7.41 In-line labelling and label printing may be used to advantage, butprinters are often noisy. Their location should be considered carefully tominimise the adverse effect of this noise. In addition, when it is necessary forstaff to read information displayed on VDU screens it is essential that theambient lighting is suitable.

Sterilizer loading area

C7.42 When single-ended sterilizers are used it is important to ensureadequate segregation of unprocessed goods from processed goods. Chemicalprocess indicators in conformity to EN 867-2 may be of value.

C7.43 Adequateto be used.

space must be available for the number and type of trolleys

Post-sterilization area

C7.44 This area provides the interface between the sterilizers and theprocessed goods store and should provide adequate space and facilities toallow product removed from the sterilizer to be inspected and to bequarantined until verification that the cycle was satisfactory.

C7.45 The area should provide space where packs may be allowed to cool toroom temperature before they are handled.

C7.46 Each pack should then be inspected to verify that the packaging is notwet or damaged and that the seal or closure is intact.

C7.47 For gas sterilization processes an additional facility to provide thecontrolled removal of residual sterilant gas may be required. After verificationthat the sterilization cycle was satisfactory and inspection of the sterilized packsthey may be transferred to the processed goods store or sent directly todespatch for immediate distribution.

Processed goods store

C7.48 The area should provide facilities where sterile packs may be storedaway from excessively humid, hot or cold locations, strong light sources andelectrical power supplies. Adverse conditions can cause deterioration of plastics,rubber and cellulosic materials found in the packaging or the contents, givingrise to embrittlement, loss of tensile strength, and so on (see SIB(7)3 ‘Storageof sterile medical devices and surgical products’, DHSS 1982).

C7.49 The storage area needs to be clean, dry and well ventilated but freefrom draughts. Ideally the environment in the store should be maintained at18-22°C with RH 35-75%.

C7.50 Storage may be on open shelves or in closed cupboards. When shelvesare used they may be solid or of wire mesh construction. The lowest shelfshould be solid and should be 25-30 cm above floor level. The top of shelvingstack should be a solid shelf 25-30 cm below ceiling level to allow room forcleaning, but should not be used for storage.

C7.51 Shelves should be located away from outside walls which can sufferfrom condensation problems, and from other sources of water such as sinks,and sprinklers.

C7.52 There should be no unlagged cold water pipes or other similar serviceswhich may cause condensation to form and drip onto packs.

C7.53 A high standard of cleanliness is required in this area. When facilitiesare less than ideal the inadequate conditions may be ameliorated by wrappingthe sterile packs in a protective dust cover such as a polythene bag duringstorage. This may then be removed immediately prior to despatch. Note that, ifpacks are to be wrapped in dust covers, they must be allowed to cool to roomtemperature first.

Materials storage

C7.54 HBN 13 Appendix 4 provides guidance on determining the spacerequired.

C7.55 A materials store is required for the storage of incoming supplies,including single use items, consumables, and new re-usable items as well aspackaging materials.

C7.56 The same store may also be used for incoming supplies ofcommercially produced supplies items (for example commercially producedsterile packs).

C7.57 The passageway between shelves or racking should be wide enough topermit proper use of handling equipment without causing damage to storedmaterials.

C7.58 Secure separate storage needs to be provided for the segregation ofdefective or non-conforming materials products.

C7.59 Facilities are required for the reception of purchased goods andsubsequent inspection and confirmation that they are supplied in accordancewith the purchase specification.

Packaging equipment

Heat sealers

C7.60 Several patterns of heat sealer are in common use:

a. Hand-operated heat sealers with scissor action jaws; many of these weredesigned for sealing light gauge polythene bags for food use and arerarely satisfactory for sterilization packaging.

b. Parallel-jaw sealers, which may be hand or foot operated, have one of thejaws heated and this presses against the opposing unheated jaw. Heat-seal packaging placed between the jaws is heated and compressed.

c. Heat-seal conveyors work in a similar manner, butmoved between heated elements of the conveyor.

items to be sealed are

C7.61 The seal integrity and strength is affectedand dwell time of the heat-sealing equipment.

by the temperature, pressure

C7.62 In order to ensure reproducible satisfactoryshould be validated, controlled and monitored.

sealing all three variables

C7.63 Many of these heat sealers are available without a built-in timer, withno reproducible control over sealing pressure and with no indication of theoperating temperature. The design of many heat sealers makes effectivemonitoring, calibration and adjustment of the operating conditions difficult.

C7.64 Any heat sealer which is to be used for sealing packs for sterilizationshould be monitored regularly for the controlling variable of temperature,pressure and dwell time. Machines which cannot be independently testedshould not be used.

Overseal crimpers

C7.65 Crimping devices for the application of crimp-on overseals may bemanual or automatic.

C7.66 The manual crimpers are available as hand-held devices or as bench-mounted, lever-operated machines.

C7.67 Most, if not all, of the manually operated crimping equipment availableis pre-set for overseals of a particular size, or has sets of change parts toaccommodate other sizes. The compressive force applied is not adjustable.

C7.68 It is essential that the crimper is only used with overseals, stoppers andcontainers of the pattern for which it is intended.

C7.69 Crimpers for applying foil caps to aluminium tubes for use insterilizers are also available. These are usually hydraulically operated.

hot air

Screw cappers - controlled torque

C7.70 Capping machines with a built-in, adjustable, torque limiter areavailable. The torque setting to be used varies with the size and type of capand the stopper or other seal being used. The settings recommended by themanufacturer of the closure should be used.

C7.71 The calibration of the torque limiting device should be verified atregular intervals.

Ampoule sealers

Manual sealing

C7.72 Although it is possible to effectively seal an ampoule without apurpose-built ampoule sealer, it is difficult to get the correct temperature,sufficiently localised and in the required time.

C7.73 Commercially available ampoule sealers use a natural gas/compressedair (low pressure of the order of 2-3 psig) or gas/oxygen flame, in burners seteither side of the ampoule.

C7.74 The ampoule stands on a support platform which is verticallyadjustable to position the flames at the required position on the ampoule

C7.75 The flames are positioned and adjusted so that the glass wall ofampoule neck is just by the points of the blue cones within the flames.

neck.

the

C7.76 The filled ampoule is rotated in the flame.

C7.77 When the glass in the heated region of the neck melts and starts tofuse the top of the ampoule is grasped with pliers or forceps and pulledupwards in a smooth but fairly rapid movement.

C7.78 This detaches the unwanted portion of the neck leaving a fused endwhich should be smooth and round without any sharp pointed protrusion or along tail of glass.

C7.79 To produce consistently successful seals requires some skill, which isonly achieved through practice and experience.

C7.80 Semi-automatic and automatic ampoule sealers reproduce the samesequence of events but the whole process is automatic.

C7.81 The flame temperature, the position of the flame, the dwell time, andthe timing and rate of detachment of the neck extremity all affect the qualityof the seal.

C8.0 Packaging operations

Routine operation, control and monitoring

C8.1 The materials, systems, equipment and procedures used should havebeen evaluated for their suitability before implementation for routine use (seeChapter C6).

C8.2 The following guidance is based on the assumption that high-speedpackaging machinery capable of handling large batches will not be used. Whenlarge batches are to be processed on such equipment the guidance andrequirements in the Regulations and Standards applicable to commercialmanufacturers should be adopted.

Documentation

C8.3 There should be written specifications for all packs giving details of boththe contents and the packaging requirements.

C8.4 The order in which the contents of composite packs should be placed,to facilitate their aseptic removal from the pack, should be documented in thepack specification and the associated packing procedure.

Packaging instructions

C8.5 There should be formally authorised packaging instructions for eachproduct, pack size and type. These should normally include or make referenceto the following:

a . the name of the product;

b . either a description of its pharmaceutical form andapplicable, or a list of the contents of the pack;

strength,where

c . the pack size expressed as the weight or volume of the product in thefinal container, where applicable;

d. a complete list of all the packaging materials required includingquantities, sizes and types, with the code or reference number relating tothe specifications of each packaging material;

e . where appropriate, an example or reproduction of the relevant printed

packaging materials, and specimens indicating where to apply any batchnumber, references and shelf life of the product;

f. any special precautions to be observed, including the order in which

components should be assembled to facilitate aseptic removal;

g . a description of the packaging operation,includingsubsidiary operations, and equipment, to be used;

any significant

h . details of in-process controls with instructionsacceptance limits, where applicable.

for sampling and

Batch packaging records

C8.6 When products are prepared in batches a batch packaging recordshould be kept for each batch or part batch processed.

C8.7 The record should carry the batch number and the quantity of bulkproduct to be packed as well as the batch number and the planned quantity offinished product that will be obtained.

C8.8 Before any batch packaging operation begins, there should be recordedchecks that the equipment and work station are clear of previous productsdocuments or materials not required for the planned packaging operations andthat the equipment is clean and suitable for use.

C8.9 The information should be entered at the time each action is taken and,after completion, the record should be dated and signed.

Packaging records for single packs

C8.10 The records kept should have a sequential batch code enabling

finished pack to the manufacturing's lot number for any single,including packaging, used in the composition of the pack.

Batch numbering

C8.11 All packs produced should have a sequential batch code enablingtraceability and, when necessary, the recall of defective product.

C8.12 The batch code used should indicate the date of sterilization, themachine used and the process log/cycle number.

C8.13 Batch numbering with sterilizer and cycle may conveniently be doneafter sterilization when inspecting each pack to ensure that it has not becomewet or sustained any damage.

Labelling

C8.14 Each sterile pack should be clearly labelled with a description of thepack contents and the description “sterile”.

C8.15 Normally filling and sealing should be followed as quickly as possibleby labelling to ensure that no mix-ups or mislabelling can occur.

C8.16 The correct performance of any printing operation (for example, codenumbers, expiry dates), whether done separately or in the course of thepackaging operation, should be checked and recorded.

C8.17 The accuracy of labelling should be checked. Special care should betaken when using individual pre-printed labels and when over-printing is carriedout off-line. Roll feed labels are normally preferable to cut labels, in helping toavoid mix-ups.

C8.18 When large batches of single product are being processed the correctnumber of bags may be labelled for each batch. On completion of thepackaging operation for each batch the number of labelled bags should bereconciled with the number of products packed and any surplus bags destroyedbefore commencement of a different product. Any pre-stamping or labelling ofbags should be controlled by documented procedures.

C8.19 Checks should be made to ensure that any electronic code readers,label counters or similar devices are operating correctly.

Control of the packaging operation

C8.20 When setting up a programme for the packaging operations particularattention should be given to minimising the risk of cross-contamination, mix-ups, substitutions, or mis-labelling.

C8.21 Before packaging operations begin, steps should be taken to ensurethat the work area and packaging equipment are clean and free from anyproducts, materials or documents previously used, if these are not required forthe current operation.

C8.22 All products and packaging materials to be used should be checked ondelivery to the packaging department for quantity, identity and conformity withthe packaging instructions.

C8.23 Containers and packaging for filling should be clean before filling;particular attention should be given to avoiding and removing anycontaminants such as glass fragments and metal particles.

C8.24 Control of the product during packaging should include at leastchecking the following:

• general appearance of the packages;

• whether the packages are complete;

• whether the correct products and packaging materials are used;

• whether the labelling, including any over-printing, is correct;

• the correct functioning of packaging equipment, for example thetemperature gauge reading on heat sealing equipment.

C8.25 All wrapping material used should be inspected for flaws, holes, tears,dirt, stains and other defects at the time of packaging by the operator using it.

C8.26 Any of these defects should be cause for rejection of the material,which should be scrapped.

Heat-sealing equipment

C8.27 Closing and sealing machines must be in good condition, properly setand maintained to the manufacturer’s specification, and closing and sealingoperations should be under constant supervision.

C8.28 For heat-sealing operations the critical variables of temperature,temperature uniformity, pressure, pressure uniformity, dwell time, and thecharacteristics of the packaging materials, for example the type, thickness anduniformity of the heat-seal adhesive, should, ideally, be verified at frequentregular intervals.

C8.29 If the available equipment does not provide the facility for routinemonitoring of the physical operating variables then routine monitoring ofprocess efficacy by checking the quality of the output should be adopted.

C8.30 The efficacy of the seals should be tested and proved on a regularbasis, not less than daily for each heat sealer.

C8.31 As a minimum daily heat-sealing records should be kept and theseshould be reviewed quarterly; there should also be a quarterly check on thetemperature control of each heat sealer.

Glass containers

C8.32 Because of the hazards associated with glass contamination it isessential that, if packing in glass takes place, suitable precautions are describedin formal documented procedures to deal with any glass breakages which mayoccur.

C8.33 Equipment for handling and processing glass containers should beadequately screened to ensure that any broken glass is contained. In particular,cleaning and filling equipment must be suitably screened and it is good practiceto fully enclose all conveyors between cleaning and closing.

C8.34 Conveyors for glass should not pass over areas where exposed productor components may be held.

C8.35 Suitable lidded containers to be used only for the disposal of brokenglass should be provided.

QC tests

C8.36 Quantitative testing of the adequacy of packaging seals and closuresrequires the use of laboratory facilities and equipment not available in mosthospitals.

C8.37 However, there are qualitative procedures that can be carried outwhich are sufficient to demonstrate a satisfactory seal, although they may be ofless value in any investigation as to the cause of an unsatisfactory seal.

C8.38 These procedures are based on visual examination which can becarried out either by the operator during the various stages of the packingoperation or by a QC inspector given that specific task.

Pinholes

C8.39 The performance of both porous and impermeable materials as abacterial barrier depends on them being free from pinholes and other similardefects.

C8.40 Laboratory tests for pinholes are baseddye solution.

on detecting the passage of a

C8.41 However, visual examination of opaque or translucent material againsta bright light is a sensitive method of detection, which may be applied in thepacking room.

C8.42 The method is unsatisfactory for transparent film. However the plasticfilm used in pouch and reel material is typically a laminate of two films. There isa very low probability of a pinhole occurring in the same spot in both films.

Inspection of seals

C8.43 A subjective assessment may be carried out by examining and openinga number of sample packs taken from production.

C8.44 Where one of the webs being sealed is transparent the uniformity ofthe seal can be examined without opening the pack. In other cases it will benecessary to peel open the seal.

C8.45 In carrying out the examination the following factors should beconsidered:

• the appearance of the seal; it should be uniform across the entire sealedsurface and should be free from creases, striations or unsealed areas;

• the seal strength; the seal should be peeled apart and attention paid towhether the force required remains constant or whether there areapparent weak spots; with practice and experience it is also possible torecognise overall increased or decreased seal strength;

• the seal characteristics; when the seal is peeled apart there should bevisible evidence of the seal on both of the webs, but there should be nospitting, tearing, delamination or fibre shedding;

• the condition of the packaging, particularly in the area of the seal;excessive pressure during heat sealing may cause damage or distortion;high temperatures or prolonged dwell times may cause scorching of thepaper web.

Packaging for sterile medicinal products

C8.46 Filled containers of parenteral products should be inspectedindividually. When inspection is done visually this should be done under suitableand controlled conditions of illumination and background.

C8.47 Operators doing the inspection should pass regular eye-sight checks,with spectacles if worn, and be allowed frequent breaks from inspection.

C8.48 When other methods of inspection are used the process should bevalidated and the performance of the equipment checked at intervals.

Process indicators

C8.49 Asystemshould be used.

to differentiate between processed and unprocessed items

C8.50 Single-use packaging materials may be obtained pre-printedprocess indicators suitable for one or more sterilization processes.

with

C8.51 For other packaging materials suitable process indicators may bepurchased printed onto adhesive packaging tape, adhesive patches or ontolabels.

C8.52 Whichever system is chosen the process indicator should conform tothe requirements of the relevant European standards (BS EN 867-l and BS EN867-2).

Sterile product release

C8.53 Post-sterilization it is necessary to verify that the sterilization cycle wassatisfactory and check that each pack is either

• labelled with a reference to the number of the sterilizer cycle throughwhich it was processed, or

• reconciled with the load manifest for the cycle, for packs which werelabelled before sterilization with a reference intended to be traceable tothe cycle number.

C8.54 Packaged sterile product should be inspected after sterilization andbefore release to ensure that the seal or closure remains intact, and that thepack is undamaged.

C8.55 The nature of the inspection will depend upon the nature of thepackaging system used.

C8.56 For example, glass ampoules may be inspected for cracks and flawsvisually, by means of a dye penetration test or by means of a corona dischargecrack detector.

C8.57 Whenever the integrity of the packaging is in doubt the sterilizedproduct, or in extreme cases the sterilizer load, should be regarded as non-sterile and not released for distribution.

Operator training

C8.58 All operators should receive training in the documented proceduresthat they will be expected to carry out.

C8.59 Particular emphasis should be placed on operator dependenttechniques such as the correct folding and closure of wraps.

C8.60 Training should Include instruction on the correct use of equipment,inspection techniques and test methods and on the intended use of theproduct.

C8.61 Training should be documented and recorded and should be reviewedperiodically.

C9.0 Storage and distribution

Shelf life

C9.1 Time-related expiry dates for the maintenance of sterility are widelyrecognised as being of little value since under artificially created worst-casestorage conditions packs such as textile wrapped packs could be shown to havebecome contaminated within 18-30 days.

C9.2 When the products were overwrapped with a dust sheet this wasextended to at least nine months, and in paper/plastic pouches was found tobe at least a year.

C9.3 Maintenance of sterility dependsconditions including such factors as:

to a great extent on the storage

• the microbial contamination of the storage environment;

• movements of air;

• movements and behavioural standard of personnel;

• environmental temperature, relative humidity;

• moisture, such as condensation;

• location in the store, etc.

C9.4 The barrier properties of the packaging material are also a contributoryfactor. The general concept is that the combination of the packaging and thecontrol exerted over storage and distribution conditions should guarantee thatthe contents remain sterile until opened for use.

C9.5 Some form of date coding may still form a convenient inventory controlsystem, means of assessing the frequency of usage and for deciding whetherunused packs are of a type which no longer need to be produced.

C9.6 The use of arbitrary expiry dating on packs should be replaced withbatch numbering and/or manufacturing date codes which can be used tofacilitate good stock rotation, based on a first-in-first-out system.

C9.7 Maintenance of sterility cannot be guaranteed once the packaging hasbeen breached and the labelling should warn the user to verify the condition ofthe packaging before opening the pack for use. A warning such as “sterileunless packaging opened or damaged” is usually sufficient.

Distribution of sterilized supplies

C9.8 Trolleys used for distribution within the hospital should be covered orclosed with a solid bottom shelf.

C9.9 Each article to be loaded onto a trolley or into a transit container shouldbe inspected and handled with care; packs should not be crushed together.Cramming additional packs into too small a space will invariably result indamage.

Storage of sterile supplies

C9.10 The function of this storage area may be limited to the storage ofpacks produced in the SSD or may also accommodate commercially producedpacks and sterile devices purchased from commercial suppliers.

C9.11 Medical equipment that has been decontaminated, disinfected,cleaned, serviced, repaired and readyfor re-issue may also be stored here.

C9.12 Sufficient space is required for loading trolleys and containersdistribution on site and for loading containers for delivery off site.

C9.13 Entry to the area should be restricted to authorised and trainedpersonnel.

for

C9.14 Staff should wash their hands before entering; where no convenientwashing facility is available, it may be acceptable to substitute treating cleanhands with an alcohol-based hand rub for washing.

C9.15 Movement of personnel within the area should be kept to the

minimum necessary.

C9.16 The floor should be cleaned regularly by damp mopping and/orvacuuming; sweeping, brushing or the use of rotary scrubbing and polishingmachines should be avoided since these may disperse contamination from thefloor as an aerosol.

C9.17 Shelves, trolleys, delivery carts and transit containers should be subjectto regular cleaning in accordance with a documented procedure and schedule.

C9.18 Packs should be spaced on shelves with sufficient room to avoidfriction or the jarring of adjacent products when one is removed.

C9.19 Rigid re-usable transit containers may be used with advantage tocontain smaller packs; these containers should also be on the cleaningschedule.

C9.20 Packs dropped on the floor should be discarded or sent for re-processing, as applicable, unless they were protected by an outer dust cover,such as a polythene bag, show no visible damage to the packaging and do notcontain items which could be damaged by impact.

C9.21 Storage arrangements should be orderly to facilitate efficient rotationof stocks, batch differentiation and ease of cleaning.

C9.22 Sterilized packs should be issued in rotation based on the First-ln–First-Out (FIFO) principle in accordance with a documented procedure.

C9.23 Sterilized packs should be handled as little as possible.

C9.24 After sterilization it is important that packs are stored safely in amanner which will assist in preserving the sterility of the contents.

Handling sterile packs

C9.25 It is important that all personnel who will be required to handle sterilepacks (porters, drivers, SSD assistants, phlebotomists, nurses, clinicians, etc)

receive appropriate trainingare necessary.

in the correct handling procedures and why they

C9.26 Many sterile packs wiII contain expensive and delicate Instruments andrequire careful handling. All sterile packs need to be handled in a mannerwhich wiII not compromise their sterile condition.

C9.27 As a minimum the following rules should apply:

a. The hands of personnel who will handle sterile packs need to be cleanand dry;

b. The sterile packs need to be kept dry and must not be torn, punctured orotherwise damaged;

c. Any packs that are visibly damaged, stained or wet should be returned tothe SSD for disposal or re-processing, as appropriate;

d. It should be possible to verify that the pack has been processed; this maybe by means of a process indicator, or by appropriate labelling such as asterilizer cycle number. Note that process Indicators do not indicate thesterility of the pack contents, only that the pack was processed through asterilizer;

Containers, distribution trolleys and any surfaces on which thebe placed must be clean and dry;

packs will

Transport and distribution

C9.28 There should be documented procedures for delivery and for thepackaging, collection and return of used goods

C9.29 Containers and trolleys should be easy to clean, properly maintainedand should adequately isolate the goods in transit from environmental hazards

C9.30 The cleaning procedure for bulk containers and trolleys should bedocumented and records should be kept of cleaning carried out

C9.31 In transit the contents of containers should be adequately identified bymeans, such as labels, which will not be erased in transit.

C9.32 Used goods being returned must be segregated from clean and sterilegoods being delivered.

C9.33 Vehicles reserved for the delivery of clean and sterile goods should beused whenever possible. If dedicated vehicles are not used then each vehicleused must be cleaned after use for the return of used goods and before use forthe transport of sterile goods.

C9.34 The cleaning procedure for the vehicle interior should be documentedand records should be kept of cleaning carried out.

C9.35 As an alternative the use of sealedfor transport in either or both directions.

Storage in clinical areas

leakproof containers may be used

C9.36 The same principles apply as were discussed for the processed goodsstore

C9.37 The storage facility should be secure, easy to clean and organised toaid stock rotation (for example a double-sided cupboard filled from the backbut where goods are removed from the front).

C9.38 The quantity of goods stored should be limited to those actuallyneeded within a reasonable time period.

C9.39 The place and method of storage varies, but it should be separateaccommodation, not a general store with bedpans, urinals etc.

C9.40 Storage should be segregated or, if it has to be shared, it should bewith other clean and/or sterile equipment.

C9.41 A high standard of cleanliness is required and packs must be kept wellaway from sinks and other sites of possible contamination.

Packaging for return of used items for re-processing

C9.42 A local policy for the handling of potentially contaminated andhazardous items, and practices for safe containment during transport back tothe SSD need to be established.

C9.43 All returned items should be regarded as potentially contaminated andthus infective.

C9.44 Containers for returning goods should be leak proof, securely closeableand safe to handle. The container design should Include the facility for clearlabelling to indicate the nature of the contents.

Glossary of terms

Bioburden

Capacity (for glass containers)

Closure

Closure integrity

Final pack

Internal pressure resistance

Microbial barrier

Multi-trip container

Packaging compatibility

Packaging material

Packaging system

Primary pack

Seal

Seal integrity

Secondary pack

Shelf pack

Shipper pack

Single-trip container

Terminally sterilized

Thermal shock resistance

Transport pack

Population of viable micro-organisms on an item.

The internal volume at 20°C.

Means used to close a package where no seal is formed, for example by repeatedfolding to construct a tortuous path.

The quality of the closure which ensures that it presents a microbial barrier

The pack in which a medical device is sterilized. In addition to the primary pack asecondary and/or transport pack may be included.

The internal hydraulic pressure which a glass container at 20°C can withstandwithout breaking

The ability to prevent the ingress of micro-organisms.

A glass container which has strength characteristics sufficient for it to withstand anumber of filling/use operations.

The ability of the packaging material and/or system to achieve the requiredperformance without detrimental effect on the medical device.

Any material used in the fabrication or sealing of a packaging system or primarypack.

One or more packaging materials assembled into a single unit intended as part or allof a primary pack.

The sealed or closed packaging system forming a microbial barrier enclosing themedical device, and (usually) in contact with the medical device.

The result of joining of layers, for example by use of adhesives or thermal fusion.

The quality of the seal which ensures that it presents a microbial barrier.

The pack containing one or more medical devices, each in its primary pack.

see Secondary pack.

see Transport pack.

A glass container designed and manufactured to be sufficiently strong to withstandonly one filling/use operation.

Descriptor for medical devices which are sterilized after being completely sealed orenclosed in at least the primary pack.

The ability of a glass container to withstand a sudden temperature change withoutbreaking.

The pack containing one or more primary and/or secondary packs intended toprovide the necessary protection during transport and storage

Ullage

Unit pack

Vacuity

Validation

That part of the contents of a container which wants for filling. Expressed in units ofvolume or as a percentage of the total container volume.

see Primary pack.

The free space left above the contents in a sealed container expressed as apercentage of the nominal volume of the contents.

Documented procedure for obtaining, recording and interpreting the data requiredto show that a process will comply with predetermined specifications.

Section D

A contract for the annual testing of sterilizers


21

Small power

Contents

Invitation to tender page 131

Price schedule page 133

Appendix A - Sterilizer inventory and unitcosts page 156

Appendix B - Testing philosophy andValue Added Tax estimation form page 134 procedures page 158

Schedule of information to besupplied by the tenderer page 135

Abstract of particulars page 136

General conditions of contract page 137Definitions

Appendix C - Annual performance tests page 160

Appendix D - Reports page 162

Appendix E - Retest request form page 168

Period of contract and determinationProcedureContract rates and pricesAccountsAssignment transfer or sub-letting of the

contractDetermination of the contract due to default orfai lure

Injury to persons: loss of propertyInsurance against injury to persons and loss of

propertyData Protection ActAdmission to the site(s)ArbitrationValue Added TaxLocal health building requirementsRacial discriminationMental Health Act

Particular specification page 151RegulationsCompliance with British StandardsObligations of the employerAccess to siteHealth and safetyFire precautionsSecurity and public health precautionsFacilities on siteWorkmanship and materialsRequisitioning of worksDocumentationDescription of the work


GENERAL CONDITIONS OF CONTRACT

FOR ANNUAL TESTING OF STERILIZERS

GENERAL CONDITIONS OF CONTRACT

1. DEFINITIONS

1.01 ‘The Contract’ means all documents forming the tender and acceptance thereof,together with the documents referred to therein, including these Conditions (exceptas set out in the Abstract of Particulars) and the Appendix.All these documentstaken together shall be deemed to form one Contract.

1.02 In the case of a discrepancy between these conditions and the Annexes forming partof the Contract Document, the Provisions of these Conditions shall prevail.

1.03 In the Contract the following expressions shall, unless the context otherwiserequires, have the meanings hereby respectively assigned to them;

1.04 ‘The Schedule(s)‘ means the Price Schedule(s) listed in the Abstract ofParticulars.

1.05 ‘The Employer’ means the NHS Trust/Employer so designated in the Abstract ofParticulars.

1.06 ‘The Contractor’ means the person or persons whose tender is accepted by theEmployer and his or their legal personal representatives or permitted Sub-Contractors and assigns.

1.07 ‘The Contract Administrator’ is the person nominated by the NHS Trust/Employerto act for the NHS Trust/Employer in Managing the Contract or any person for thetime being acting for him/her for the purpose of the Contract. Nominatedrepresentatives are listed in the Abstract of Particulars.

1.08 ‘The Authorised User’ means the person responsible for the Management of theHospital Department in which the Sterilizer is installed.

1.09 ‘The Work’ means the work for the performance of which the Contract provides.

1.10 ‘Unscheduled Work’ means the work carried out by the Contractor at the requestof the Contract Administrator which does not form part of the Work.

1.11 ‘The Site(s) means the grounds, buildings and/or installations within or without thebuildings in or at which the work is to be performed under the Contract (SeeInventory - Appendix A).

1.12 ‘The Contract Period’ means the period commencing on the date indicated in theinvitation to Tender and continuing until a date 5 years thereafter or until suchearlier date at which the Contract may have been determined by either party inaccordance with Condition 2 and 7 hereof or by the Employer in accordance withCondition 10 hereof.

1. DEFINITIONS (Continued)

1.13 The proper law of the Contract shall be English Law.

1.14 Any decision to be made by the Employer under the Contract may be made by anypersons authorised to act for them for that purpose and may be made in suchmanner and on such evidence or information as such person or persons shall thinkfit.

1.15 The headings to the Conditions shall not affect the interpretation thereof.

1.16 Any notice required to be given under this Contract shall be in writing and shallbe delivered or posted by recorded delivery to the last known place or abode orbusiness of the Contractor or, if the Contractor is a Company, to the registeredoffice of the Company, in which case the notice shall be deemed to have been dulyserved at the time it is delivered.

2. PERIOD OF CONTRACT AND DETERMINATION

2.01 The Contract shall remain in force for a minimum period of 1 year and amaximum period of 5 years from the date for the commencement of the Contractas stated in the Invitation to Tender, subject to the due performance by theContractor of his obligations under the Contract and without prejudice to thespecific rights of the parties of determination thereunder.

2.02 The Contract may be determined (without prejudice to the Contractor’s orEmployer’s rights under Conditions 7 and the Employer’s rights under Condition10 hereof) at the end of the 1 year minimum period or at any time thereafterprovided 13 weeks notice to that effect shall have previously been given by eitherparty.

3. PROCEDURE

3.01 Subject to the provision of the Contract, the Contractor shall carry out the Workrequired in accordance with the Contract and to the satisfaction of the ContractAdministrator at the times set out in the Schedule or at such other times as theEmployer may from time to time direct and, so as not to interfere with the normalcarrying out of business of the Employer’s staff in occupation of premises inwhich the Work is being carried out.

3.02 The Employer may from time to time by notice in writing subject to the agreementof the Contractor (which shall not unreasonably be withheld) vary the Contract by:

3.

4.

4.01

PROCEDURE (Continued)

A. The deletion from the Inventory of the name and particulars of any site andthe price payable for the work in respect thereof. If the Contract price forthat item is an annual price, the amount to be paid to the Contractor inrespect of the work satisfactorily performed up to that date specified in suchnotice shall be calculated pro-rata to the annual price.

B. The addition to or the reduction in the items of work, plan and/or equipmentat any of the site(s) referred to in the said Inventory and in the event of suchvariation a fair and reasonable adjustment of the price payable for such itemsof work at that site shall be agreed with the Contractor.

CONTRACT RATES AND PRICES

NB Conditions 4.01 and 4.02 applicable as stated in the Abstract of Particulars.

The Contract Rates and Prices quoted in the Schedule and agreed by the Employershall be subject to adjustment on each successive anniversary of the date ofcommencement of the Contract Period in accordance with the formula set outbelow:

For this purpose, the reference in this Condition to an Index refers to theappropriate Index indicated in the Health Services Price Index forEngineering Maintenance Contracts issued by the Department of Health,Richmond House, 79 Whitehall, London, SW 1A 2NS, and ‘index numbers’means the index numbers contained therein.

FORMULA

X = Y ab

Where:

X =Y =a =

The required adjusted Contract Rate or PriceThe Contract Rate or Price that is required to be adjustedThe index indicated for the month during which commenced the first dayof the second or subsequent years for which the revised Contract Rate orprice is to be calculated.

b = The Base Index for the month during which the Contract Periodcommenced.

4. CONTRACT RATES AND PRICES (Continued)

4.02

5.

The Contract Rates and Prices quoted in the Schedule shall apply to all the workwhich is required to be carried out under the Contract in accordance withConditions 3.01 hereof, but either party may give notice under Condition 2.02hereof to terminate the period within which the Contract Rates and Prices areapplicable with a view to negotiating a revision in the said Rates and Prices. TheEmployer will not, however, be obliged to consider an increase in the ContractRates and Prices to take effect in respect of the work which is required to becarried out before the end of the first year of the Contract period, or to negotiate asubsequent increase in the Contract Rates and Prices to take effect in respect of thework which is required to be carried out within a period of 12 months following aprevious increase, save in circumstances, accepted by the Employer as beingexceptional.

ACCOUNT

5.01 Invoices shall be rendered monthly within 14 days after the end of the month to theContract Administrator.

5.02 Payment of fixed charges for ordinary testing will be made as soon as the invoicesfor the month can be examined and approved by the Employer. They will only beconsidered for payment, however, after receipt of the test results of thoseSterilizers that have been satisfactorily tested and invoiced.

5.03 Accounts for retesting or Unscheduled Work ordered by the ContractAdministrator will be paid as soon as possible after examination of test resultsand invoices and certification by the Contract Administrator.

6. ASSIGNMENT, TRANSFER OR SUB-LETTING OF THE CONTRACT

6.01 The Contractor shall not, without the written consent of the Employer whoseconsent shall not unreasonably be withheld, assign or purport to assign hisobligations hereunder or enter into any Sub-Contract in respect of any portion ofthe work.

6.02 The Contractor shall be responsible for any Sub-Contractor employed by him inconnection with the Work.

6.03 The Contractor shall make good any loss suffered or expense incurred by theEmployer by reason of any default of failure, whether total or partial on the partof any Sub-Contractor.

7. DETERMINATION OF THE CONTRACT DUE TO DEFAULT OR FAILUREOR CORRUPTION

7.01 If materials and workmanship of the quality and standards specified have beenused in carrying out the work or any part thereof is otherwise not in accordancewith the Contract and if the Contractor, having been given by the Employer anotice in writing to rectify, reconstruct or replace any defective work or a noticein writing that the work is being performed in an inefficient manner, shall omit tocomply with the requirements of such notices for a period of 7 days thereafter, or,if the Contractor shall fail to carry out the work during any period stated in theSchedule or otherwise as the Employer shall have directed or required, theEmployer shall have the right to;

A. i. Have such unsatisfactory materials or workmanship or uncompletedwork replaced, rectified or completed by persons other than the Contractorand to recover from the Contractor any cost incurred thereby in excess ofthe amount which would have been payable under the Contract for suchwork, or

ii. Determine the Contract immediately and any costs or expenses incurredthereby, from the day of such determination until the first day thereafterupon which the Contractor, but for such determination, could havedetermined the Contract under Condition 2.02 hereof, shall, so far as theyexceed the sums which would have been payable under the Contract forthat period, be chargeable to and recoverable from the Contractor by theEmployer.

B. i. If the Contractor makes a composition or arrangement with his creditors, orbecomes bankrupt, or being a company makes a proposal for a voluntaryarrangement for a composition of debts or scheme or arrangement to beapproved in accordance with the Companies Act 1985 or the Insolvency Act1986 as the case may be or any amendment or re-enactment thereof, or

has a provisional liquidator appointed, or

has a winding-up order made, or

passes a resolution for voluntary winding-up (except for the purposes ofamalgamation or reconstruction), or

under the Insolvency Act 1866 or any amendment or re-enactment thereofhas an administrator or an administrative receiver appointed.

142

7. DETERMINATION OF THE CONTRACT DUE TO DEFAULT ORFAILURE OR CORRUPTION (Continued)

offer or give or agree to give to any person any gift or consideration of anykind as an inducement or reward for doing or forbearing to do or for havingdone or forborne to do any action in relation to the obtaining or execution ofthis or any other contract with the Employer, or for showing or forbearing toshow favour or disfavour to any person in relation to this or any othercontract with the Employer, or if the like acts shall have been done by anyperson employed by the Contractor or acting on his behalf (whether with orwithout the knowledge of the Contractor), or if in relation to this or anyother contract with the Employer the Contractor or any person employed byhim or acting on his behalf shall have committed an offence under thePrevention of Corruption Acts to 1916.

7.02 The Contractor may without prejudice to any other rights and remedies that he maypossess, by notice in writing determine the Contract if the Employer has not paidwithin 28 days of receipt of an invoice from the Contractor any amount properlypayable to the Contractor by the Employer, and having been given notice by theContractor shall fail to comply with such notice within seven days from the servicethereof.

7.03 Any dispute or different of opinion arising in respect of either the interpretation oreffect of 7.02 or of the amount recoverable hereunder the Employer from theContractor shall be decided by the Employer, whose decision on that matter shallbe final and conclusive.

8. INJURY TO PERSONS : LOSS OF PROPERTY

8.01 This condition applies to any personal injury or loss of property which arises outof or in any way in connection with the execution or purported execution of theContract.

8.02 Subject to the following provisions of the Condition, the Contractor shall:

A. Be responsible for and reinstate and make good to the satisfaction of theEmployer, or make compensation for, any loss of property suffered by theEmployer to which this Condition applies;

B. Indemnify the Employer and servants of the Employer against all claims andproceedings made or brought against the Employer or servants of theEmployer in respect of any personal injury or loss of property to which thisCondition applies and against all costs and expense reasonably incurred inconnection therewith;

8. INJURY TO PERSONS: LOSS OF PROPERTY (Continued)

C. Indemnify the Employer against any payment by the Employer in order toindemnify in whole or in part a servant of the Employer against any suchclaim, proceedings, costs of expenses; and

D. Indemnify the Employer against any payment by the Employer to a servantof the Employer in respect of loss of property to which this Conditionapplies suffered by that servant of the Employer and against any paymentmade under any Government provision in connection with any personalinjury to which this Condition applies suffered by any servant of theEmployer.

8.03 If the Contractor shows that any personal injury or loss of property to which thisCondition applies was not caused nor contributed to by his neglect or default or bythat of his servants, agents or Sub-Contractors, or by any circumstances within hisof their control he shall be under no liability under this Condition, and if he showsthat the neglect of default of any person (not being his servant, agent or Sub-Contractor) was in part responsible for any personal injury or loss of property towhich this Condition applies, the Contractor’s liability under this Condition shallnot extend to the share in the responsibility attributable to the neglect or default ofthat person.

8.04 A. The Employer shall notify the Contractor of any claim or proceeding madeor brought in respect of any personal injury or loss or property to which thisCondition applies.

B. If the Contractor admits that he is liable wholly to indemnify the Employerin respect of any such claim or proceeding, and the claim or proceeding isnot an excepted claim, he, or, if he so desires and it is agreed with theEmployer his insurers, shall be responsible (subject to the condition imposedby the following sub-paragraph) for dealing with or settling that claim orproceeding.

C. If in connection with any such claim or proceeding with which theContractor or his insurers are dealing, any matter or issue shall arise whichinvolves or may involve any privilege or special right of the Employer(including any privilege or right in relation to the discovery or production ofdocuments) the Contractor or his insurers shall before taking any actionthereon, consult the legal adviser or the Employer and act in relation theretoas may be required by the Employer, and if either the Contractor or hisinsurers fail to comply with this sub-paragraph, sub-paragraph B. above shallcease to apply.

D. For the purpose of this paragraph ‘an excepted claim’ means a claim orproceeding in respect of a matter failing to be dealt with under aGovernment provision, or a claim or proceeding made or brought by oragainst a servant of the Employer.

8. INJURY TO PERSONS: LOSS OF PROPERTY (Continued)

8.05 Where any such claim or proceeding as is mentioned in paragraph B. or C. of thisCondition is settled otherwise than by the Contractor or his insurers, he shall notbe required to pay by way of indemnity any sum greater than that which would bereasonably payable in settlement having regard to the circumstances of the case andin particular to the damage which might be recoverable at law.

8.0 6 In this Condition;

A.

B.

C.

D.

The expression ‘loss of property’ includes damage to property, loss ofprofits and loss of use;

The expression ‘personal injury’ includes sickness and death;

The expressions ‘servant of the Employer’ and ‘servants of the Employer’include persons who are servants of the Employer at the time when apersonal injury or loss of property to which this Condition applies occurs,notwithstanding that they cease to be such before any payment in respect ofthe personal injury or loss of property is made, and, where they have ceasedto be such by reason of their deaths, include their personal representatives:and

The expression ‘Government provision’ means any statue, warrant order,scheme, regulations or conditions of service applicable to a servant of theEmployer making provision for continuance of pay or for payment of sickpay, or any allowance -to or for the benefit of servants of the Employer,or their families, or dependants during or in respect of sickness, injury ordisablement suffered by such servants.

9. INSURANCE AGAINST INJURY TO PERSONS AND LOSS OF PROPERTY

9.01 Without prejudice to his liability to indemnify the Employer under Condition 8 theContractor shall, throughout the Contract Period, maintain and shall cause anySub-Contractor to maintain such insurances as are necessary to cover the liabilityof the Contractor or, as the case may be, of such Sub-Contractor, in respect of thematters specified in Condition 8. The insurance in respect of claims for personalinjury, sickness or death of any person under a Contract of service orapprenticeship with the Contractor or the Sub-Contractor, as the case may be, andarising out of had in the course of such person’s employment, shall comply withthe Employer’s Liability (Compulsory Insurance) Act 1969 and any statutoryorders made thereunder or any amendment or re-enactment thereof .For all otherclaims to which this Condition applies the insurance cover shall be &5,000,000 (orsuch greater sum as the Contractor may choose) for any one occurrence or seriesof occurrences arising out of one event.

9. INSURANCE AGAINST INJURY TO PERSONS AND LOSS OFPROPERTY (Continued)

9.02 The Contractor shall, at the request of the Employer, produce and shall cause anySub-Contractor to produce, for inspection by the Employer, documentary evidencethat the insurances required by Condition 9.01 are properly maintained.

9.03 Should the Contractor or any Sub-Contractor make default in maintaininginsurances as provided in Condition 9.01 the Employer may itself insure againstany risk in respect of which the default has occurred and may charge the cost ofsuch insurance to the Contractor.

10. DATA PROTECTION ACT

10.01 Indemnity to Employer

If during the subsistence of this Contract the Contractor or any sub-contractor, orany employee servant or agent of them, is furnished by the Employer with, orotherwise obtains (with or without the knowledge or consent of the Employer),access to confidential or personal or commercial data owned or held by theEmployer upon any medium either in relation to the Employer’s own affairs orthose of others, and at any time either directly or indirectly discloses or copies ormakes improper use of any such data to a third party or allows a third partyunauthorised access to them or if the Contractor or any sub-contractor, or anyemployee, servant or agent of them, is responsible for or causes the loss, damageor destruction of all or any such data, the Contractor shall be liable in damages forany loss or damage suffered by the Employer and shall indemnify the Employeragainst all or any claims, proceedings, costs or expenses to which the Employermay be or become liable at the suit of any third party in respect thereof.

11. ADMISSION TO THE SITE(S)

11.0l The Employer may give to the Contractor notice that such persons as it mayidentify whether by name, description or employment or otherwise are not to beadmitted to the Site(s).

11.02 The Contractor shall take alladmitted to Site(s).

reasonablesteps to ensure that such persons are not

11.03 Subject to the provisions of sub-paragraphs 11.0l and 11.02 above and if andwhen directed by the Contractor shall furnish a list of names and addresses of allpersons who are or may be at any time concerned with the Work or any partthereof, specifying the capacities in which they are so concerned, and giving suchother particulars as the Contract Administrator may reasonably require.

11.04 The decision of the Employer as to whether any person is to be admitted to theSite(s), and as to whether the Contractor has furnished the information or taken thesteps required of him by this Condition shall be final and conclusive.

12. ARBITRATION

12.0 1 All disputes, differences or questions between the parties to the Contract withrespect to any matter or thing arising out of or relating to the Contract, other thana matter or thing as to which the decision or report to the Employer or of anyother person is by the Contract expressed to be final and conclusive shall afterwritten notice by either party to the Contract to the other of them be referred to asingle Arbitrator agreed for the purpose, or in default of such agreement to beappointed at the request of the Employer by the President of such one of thefollowing the Employer may decide:

A. The Law Society

B. The Institution of Civil Engineers

C. The Institution of Mechanical Engineers

D. The Institution of Electrical Engineers

E. The Royal Institution of Chartered Surveyors

* (Delete as applicable)

Unless the parties otherwise agree, such reference shall not take place untilafter the termination of determination of the Contract, or abandonment ofthe Works.

12.0 2 Such reference shall in the case of the Contract being subject to English Law bedeemed to be a submission to arbitration under the Arbitration Acts 1950 and1979, or any statutory modification or re-enactment thereof.

13. VALUE ADDED TAX

13.0 1 The Contractor shall determine whether Value Added Tax is chargeable on any orall of the goods, and services to be supplied under this Contract, and shall add theproperly calculated amount of Value Added Tax to the tax invoice or otherdocument submitted for the supplies made, in accordance with the conditionspublished by HM Customs and Excise.

14. LOCAL HEALTH BUILDING REQUIREMENTS

14.0 1 The Contractor and his employees shall comply with all relevant localrequirements for working conditions in each Health Building within the ContractArea.

15.

15.01

15.02.

16.

16.01

16.02

16.03

RACIAL DISCRIMINATION

The Contractor shall not unlawfully discriminate within the meaning and scope ofthe provisions of the Race Relations Act 1976 or any statuary modification or re-enactment thereof relating to discrimination in employment.

The Contractor shall take all reasonable steps to ensure the observance of thepreceding paragraph by all servants, employees or agents of the Contractor and allsub-contractors.

MENTAL HEALTH ACT

The Contractor shall take all reasonable steps to ensure the observance of the MentalHealth Act 1959 as repealed by the Mental Health Act 1983 or any statutorymodification or re-enactment thereof by all servants, employees or agents of theContractor and all Sub-Contractors, e.g. 16.02 to 16.05.

Patients within these Hospitals, however they may appear and behave may bereceiving treatment for mental disorder under the terms of the Mental Health Act1983. The following regulations therefore apply to everyone working on theHospital premises - whether engaged on the staff of the Health Employer, or bycontractors working within the Hospital.

Ill treatment of patients (Section 127, Mental Health Act 1983).“It shall be an offence for any person who is an officer on the staff of, or otherwiseemployed in, or who is one of the Managers or, a hospital or mental nursing hometo ill-treat or wilfully to neglect a patient for the time being receiving treatment formental disorder as an in-patient in that hospital or home; or to ill-treat or wilfully toneglect, on the premises of which the hospital or home forms part, a patient for thetime being receiving such treatment there as an out-patient.”

Any person guilty of an offence under this Section shall be liable:-

(a) “On summary conviction, to imprisonment for a term not exceeding sixmonths or to a fine not exceeding the statutory maximum, or to both”.

(b) “On conviction on indictment to imprisonment for a term not exceeding twoyears. or to a fine of any amount or to both”.

16. MENTAL HEALTH ACT (Continued)

16.04 Sexual Offences - Section 128, Mental Health Act 1959 (not repealed by MentalHealth Act 1983). Also Section 128(5) Sexual Offences Act 1956

“Without prejudice to Section seven of the Sexual Offences Act 1956, it shall be anoffence for a man who is an officer on the staff of or is otherwise employed in, oras one of the Managers of, a hospital or mental nursing home to have unlawfulsexual intercourse with a woman who is for the time being receiving treatment formental disorder in that hospital or home, or to have such intercourse on thepremises of which the hospital or home forms part with a woman who is for thetime being receiving such treatment there as an out-patient”.

Any person found guilty of an offence under this Section shall be liable onconviction on indictment to imprisonment for a term not exceeding two years.

16.05 Financial Transactions.

No member of staff, or staff of Contractors working on the premises, is permittedto enter into any financial transactions or arrangements with any patient.

PARTICULAR SPECIFICATION FOR THE ANNUAL

TESTING OF STERILIZERS

PARTICULAR SPECIFICATION

1. REGULATIONS

1.01

1.02

All work shall be carried out in accordance with.

All relevant Acts or Parliament, statutory instruments and regulations.

Any public health, security and conduct requirements as from time to time be

1.03

issued to the Contractor by the Employer.

Any relevant Safety Regulations published by the Employer copies of which areavailable from the Contract Administrator.

2.

2.01

COMPLIANCE WITH BRITISH STANDARDS

All work and material shall company with relevant European and British Standardsand Codes of Practice.

3. OBLIGATIONS OF THE EMPLOYER

The Employer shall be responsible for:

3.01 The keeping of each item of Mechanical and Electrical Plant in such a conditionthat its functions in accordance with the requirements of HTM 2010, BS3970,BS2646 and BS3421.

3.02 Arranging for statutory inspections to be carried out (under a separate contract).

3.03 Maintenance of a record for each item of Mechanical and Electrical Plant inaccordance with the requirements of HTM 2010.

This shall contain details of all maintenance and remedial works carried out oneach item of equipment to the following standards:

A. Failures DateSymptoms of failure

B. Visits by otherContractors

DateDetails of Work carried outincluding details of tests andreplacements.Date and time of completion

C. Statutory InspectionsDateDetails of any remedial work required.Signature of competent person carrying outinspection.

4.

4.01

4.02

4.03

4.04

4.05

5.

5.01

5.02

5.03

ACCESS TO SITE

The expression ‘normal working hours’ in this Contract means the hours between0800 and 1700 Monday to Friday (except Bank and Public Holidays). All othertimes are referred to as ‘outside normal working hours’.

So far as practicable the Contractor shall arrange for routine visits to be madeduring normal working hours, if it is necessary for a routine visit to be madeoutside these hours the prior agreement of the Contract Administrator must beobtained. No extra payment will be made for routine visits carried out outsidenormal working hours unless these have been specifically requested by theContract Administrator.

Access to the site is to be only by those routes indicated by the ContractAdministrator and vehicles may only be parked in those areas designated by theContract Administrator.

During normal working hours the Contractor’s staff must report to the LocalLiaison Officer or his deputy which Plant they will be working on. On completionof their task the Contractor’s staff must on each occasion enter the necessary detailsin the Plant History Record and inform the Representative that they have completedtheir task.

Outside normal working hours the Contractor’s staff must report to the mainreception desk when they must inform the duty personnel of the reason for theirvisit. On completion of their task the Contractor’s staff must on each occasionenter the necessary details in the he Plant History Record and inform main receptiondesk before leaving the site.

HEALTH AND SAFETY

It is essential that equipment is rendered and kept safe whilst it is being worked on.Also that protective clothing and other safeguards are worn and used whennecessary.

Working areas associated with sumps, pits, wells, manholes etc must be guardedand warning notices displayed. The Contractor must ensure that any of his staffrequired to enter a confined space are made aware of the guidance contained in theHealth and Safety Executive Note GS5 ‘Entry into confined spaces’ and mustfollow (so far as reasonably practicable) the recommendations contained therein.steps, ladders, equipment plan or things employed in the execution of this contractshall be adequate for their purpose and be free from defects.

The requirements of the Health and Safety at Work etc 1974 must be observed atall times.

6. FIRE PRECAUTIONS

6.01 The Contractor must ensure that he, his employees and sub-contractors complywith the provisions of Section 1 of the Standard Fire Precautions P5 (1980Edition) published by Her Majesty’s Stationery Office.

6.02 All combustible refuse, eg shavings, packing materials, etc must always becollected and removed from the site as soon as practicable.

6.03 If at any time the Contractor, his employees or Sub-Contractors notice anything thatthey consider could be a potential fire risk they must report this to theContract Administrator.

7. SECURITY AND PUBLIC HEALTH PRECAUTIONS

7.01 Certain areas are subject to special security precautions. These areas are listed inthe Abstract of Particulars.

7.02 Certain areas are subject to special public health precautions. These are listed inthe Abstract of Particulars.

8. FACILITIES ON SITE

8.01 The Employer will supply electricity, for use by the Contractor from 240 volt13 amp socket outlets placed within reasonable reach of each item of plan at no costto the Contractor.

8.02 The Contractor’s staff may use the toilet, washroom and canteen facilities providedfor staff use at the site.

8.03 Any other facilities for the works must be provided by the Contractor.

9.00 WORKMANSHIP AND MATERIALS

9.01 The Contractor shall be responsible for providing all tools, equipment andinstruments necessary for the complete execution of the work. This is to includeprovision of 3 sets of Huckaback Towels to the requirements of HTM 2010,Part 3, Chapter 13, Paragraph 13.39 -13.56.

9.02 The Contractor is required to provide labour of the requisite standard ofworkmanship at all times in connection with this Contract. The work shall beexecuted in a workman like manner and to the satisfaction in all respects of theContract Administrator. If any workmanship does not so accord the same shall atthe cost of the Contractor be rectified or replaced as instructed by the ContractAdministrator. The Contractor shall, if required by the Contract Administrator,provide evidence of a workman’s competence.

10. REQUISITIONING OF WORKS

10.01 The Persons from whom the Contractor will be required to accept requisitions atattend any urgent or necessary recommissioning are listed in the Abstract ofParticulars.

10.02 All requisitions for emergency action will be made by telephone to theContractor’s office or central control point and will be confirmed in writing within7 days by the Contract Administrator.

11. DOCUMENTATION

11.01 The Contractor must ensure that on each occasion his staff enter the details of anywork carried out on the plant in the Plant History Record before leaving the site.

11.02 The Contractor, within 14 days of the completion of the tests, shall supply theContract Administrator with a Test Report carried out under this contract asdetailed in Appendix D, together with 3 copies.

12 DESCRIPTION OF THE WORK

12.0l The Contractor shall undertake annual tests as described in Appendix B - TestingPhilosophy & Procedures and Appendix C - Annual Performance Tests on thoseSterilizers listed in Appendix A - Sterilizer Inventory.

12.02 The Contractor shall employ persons, experience, qualified and preferablycertificated to a minimum City and Guilds standard, who would be competent toperform all the required tests, documentary evidence of this shall be provided. TheEmployer may require the said persons to demonstrate his/her competence byperforming a test laid down by the Contract Administrator, to be witnessed byContract Administrator or his/her nominated representative, prior to the letting ofthe Contract or during the period of the Contract.(City and Guilds courses inSterilizer Testing Technology are available at the N.H.S.T.A. at Eastwood Park,Falfield, Glos).

12.03 The Contractor shall demonstrate that he has all the necessary equipment which isdetailed in Chapter 6, Paragraph 6.1 - 6.63 of the current edition of HealthTechnical Memorandum 2010 (HTM) and the means of calibrating them.

Current certification of accuracy traceable to the National Physical Laboratory willbe required.

12. DESCRIPTION OF WORK (Continued)

12.04 The Contractor shall prepare a schedule of the order and time in which he wouldperform the tests on the Sterilizers listed in Appendix A, to be agreed by theContract Administrator prior to the awarding of the Contract.

12.05 The Contractor will confirm his intention to perform the scheduled test with theContract Administrator or his/her nominated representative 14 days in advance.

12.06 The Contract Administrator or his nominated representative will arrange for theLocal Maintenance Engineer to be available to rectify any faults which theContractor identifies during the test.

12.07 The Contractor shall on completion of an annual test, make a signed and dated entryin the Plant History Record that the Sterilizer complies or does not comply, with theperformance requirements.In the event of non-compliance the Contractor shallnotify the Contract Administrator or his local nominated representative within 24hours.

12.08 The Contractor shall issue to the Contractor Administrator, or his/her nominatedrepresentative, within 21 days of any test being carried out, the results of the tests ina test report as demonstrated in Appendix D together with 3 copies.

12.09 The Contractor shall inspect the Plant History Records of each Sterilizer to ensurethat the service maintenance records, and where appropriate, the microbiologicalrecords are kept for all routine tests and ascertain they have been performed on eachSterilizer throughout the previous year. Comments shall be included in the Testreport.

12.10 The Contractor shall nominate on the “Invitation to Tender Form” Sheet 2 a personwho will act for the Contractor to liaise with the Contract Administrator on allmatters relating to the Contract.

12.11 The Contractor will take up any problems of the Contract with the ContractAdministrator or his/her nominated representative.

12.12 The Contract Administrator or his/her nominated representative may visit any site atany time to inspect the Contractor’s test procedures and results.

12.13 The Contractor when requested, on the appropriate form (See Appendix E) will berequired to retest any sterilizer that has not satisfactorily passed the annual testcriteria.

Repeat tests will be paid for at not more than the cost of the test of the saidSterilizer as listed in Appendix A.

12.14 The Contractor shall carry out the retesting of Sterilizers where applicable within 2working days of receiving the request.

STERILIZER INVENTORY AND UNIT COSTS

TESTING PHILOSOPHY AND PROCEDURES

TESTING PHILOSOPHY & PROCEDURES

The Testing of Sterilizers required under the contract are those called for in the HealthTechnical Memorandum No. 2010, Part 3 (HTM 2010).

The relevant clauses required for the execution of this contract in fulfilling the proceduresfor annual testing are presented in full in Appendix C.

Calibration of Instruments

It is the Contractors responsibility to ensure that all instruments used in executing the workare suitably calibrated and hold current certificate of calibration clearly traceable toNational Physical Laboratory, British Accreditation Service and that the test systemcalibration is checked immediately before and immediately after each annual test and ‘isrecorded and included in each Test Report. Copies of current certificates are to beforwarded to the Contract Administrator.

Test Equipment

The relevant clauses required for compliance of equipment used for sterilizer testing arethose called for in the Health Technical Memorandum No. 2010 Part 3 (HTM 2010)Chapter 6, Pages 35-44.

ANNUAL PERFORMANCE TESTS

YEARLY AND REVALIDATION TESTS

The tests are listed in the Health Technical Memorandum 2010, Part 3, Chapters 7 - 19.

The results of tests done should be recorded in the Plant History Record for each sterilizerin the form of a report as described in Appendix D.

This contract requires only the yearly tests to be carried out on those Sterilizers which arelisted in HTM 2010, Part 3, Chapters 4 - 5 (Check the relevant detail in Schedule ofperiodic tests to establish those tests only required for yearly testing in the tables).

The Contractor shall include in his report to the Contract Administrator if he becomesaware that the daily, weekly or quarterly tests have not been satisfactorily carried out.

Schedule of Periodic Tests. Reference HTM2010 Part 3.

R E F E R E N C E

HTM 2010 PART 3 SCHEDULE OF TEST

C H A P T E R

4 5STERILIZER PROCESS TYPE VALIDATION

TABLEPERIOD TEST

TABLE

Porous Load 2a 4a

F l u i d s 2b 4b

Unwrapped Instrument and Utensil 2c 4c

Dry Heat 2d 4d

Low Temperature Steam and 2e 4e

Low Temperature Steam and Formaldehyde 2e 4e

Ethlylene Oxide 2f 4f

L a b o r a t o r y 3a 5a

Laboratory Culture Media Preparators 3b 5b

REPORTS

R E P O R T S

Each annual test carried out must be fully reported in the format shown.

Each report will consist of:

1. T i t le page wi th detai ls of NHS Trust or Hospi ta l , Department,

Manufacturer, Steril izer type, References and date of test and person(s)

carrying out the test.

2 . Sequence Test Sheet listing each test carried out, a brief statement on test

result and any adjustments or actions taken.

3. Test Report Sheet giving detailed analysis of the test carried out with a

conclusion and recommendations.

4 . Test Sheets showing details of test carried out (See specimen test sheets).

N O T E : Test sheets may be replaced by suitable computer printouts providing they

are author ised by Contract Administrator .

5 . Associated test recorder thermocouple charts, including calibration checks,

ster i l izer recorder charts, and/or pr int-outs, Bowie/Dick sheet where

appl icable. Al l annotated and sui tably ident i f ied.

6. Each reports must be suitably bound and forwarded to the Contract

Administ rat ion together wi th 2 copies.

1. TITLE PAGE

STERILIZER ANNUAL TEST REPORT

NHS TRUST/EMPLOYER ...............................................................

HOSPITAL .......................................................

DEPARTMENT ...........................................................

MANUFACTURER .......................................................

MACHINE TYPE .......................................................

REFERENCE .......................................................

FILE REF .......................................................

TEST DUE NO LATER THAN .................................19..

DATE OF TEST .......................................................

TEST CARRIED OUT ....................................................

SIGNATURE ....................................................

2. TEST SEQUENCE SHEET

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .NHS TRUST/EMPLOYER

Hospital: Department:

Manufacturer: Ref No:

Date Tested:

Our Ref orFile No:

SEQUENCE OF TEST

NO. TEST UNDERTAKEN PASS/FAIL COMMENTSBRIEF STATEMENT

1. ......................... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

2 . ......................... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

3. ............................ ....................................

4. ............................ ......................................

5. ............................... ......................................

ETC.

...............................

...............................

...............................

.................................

...............................

...............................

...............................

...............................

...............................

...............................

.................................

...............................

...............................

...............................

.................................

3. TEST REPORT SHEET

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .NHS TRUST/EMPLOYER

Hospital: Department:

Manufacturer: Ref No:

Date Tested:

Our Ref orFile No:

1. DETAIL REPORT

Detailed report of findings as to conforming to standards, faults found,action taken, and recommendations.

2. RECORDS

HTM 2010 APPENDIX 3. Thermometric Charts/Data Logged/SummarySheets for process typeStatement on findings of Plant History Record regarding Maintenance andPeriodic Testing status.

CONCLUSIONS3.

Brief statement from above detailed report.

4. TESTER’S NAME

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

5. TESTER’S SIGNATURE

. . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

6. DATE

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

4. SPECIMEN TEST SHEETS REFERENCES

UNWRAPPED INSTRUMENT & UTENSIL STERILIZER REF 46/130V

POROUS LOAD STERILIZER REF 46/129V

FLUIDS STERILIZER REF 46/132V

DRY HEAT STERILIZER

LABORATORY REF 46/133

LOW TEMPERATURE STEAM WITH AND WITHOUT FORMALDEHYDE

(The above test sheets are D.O.H. approved and are available fromPrinting Services,NHS Supplies Authority,South & West Division,St. Modwen Road,Parkway Industrial Estate,PLYMOUTH PL6 8LH.)

LABORATORY - MEDIA

RETEST REQUEST FORM

STERILIZER PERIODIC TESTING

REQUEST FOR RETEST

CONTRACT NO.. . . . . . . . . . . . . . . . . . . . . . .

Request for Retest Form No. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

FROM: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .NHS TRUST HEALTH EMPLOYER

TO: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .CONTRACTS

Request for retesting following rectification of faults:

TRUST/EMPLOYER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

HOSPITAL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

CLINIC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

STERILIZER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

PLANT NO. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

DEPARTMENT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

ROOM NUMBER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Signature of Contracts Manager or Liaison Persomrel: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Date of request: . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Note: The retesting following any remedial works shall be carried out within three working daysof receiving notice, unless requested later.

Section E

Procedures for determining the sound power

generated by a sterilizer


Contents

E.1 Introduction page 175

E.4 Apparatus page 175

E.6 Test procedure page 177

E.13 Test result page 177


E.0 Procedures for determining thesound power generated by asterilizer

Introduction

E.1 This test, to be carried out by the manufacturer of a sterilizer, is based onthe test in Appendix D of BS 3970: Part 1: 1990 and in Section 23 of EN 285.

E.2 Except where otherwise stated here, the sound power levels of sterilizersare determined by the method described in BS 4196: Part 6: 1981 (equivalentto ISO 3746: 1979) The information given here is by itself not sufficient topermit the test to be carried out by personnel unfamiliar with the requirementsof BS 4196.

E.3 Measurements made by this method have a standard deviation of up to 5dB for discrete tone sources and up to 4 dB for wide-band noise sources. Theuncertainties can be minimised by careful consideration of the conditions inwhich the test is carried out.

a. The environmental correction factor, K, depends on the relative sizes ofthe sterilizer and the test room and the sound absorbing qualities of theroom. For a given sterilizer, the larger the room the smaller the value ofK. Although EN 285 specifies that K should be less than 7 dB, this is arelatively high value and the manufacturer should aim to achieve K = 2dB or less. This figure can normally be achieved by carrying out the test ina sufficiently large room. The assembly hall in which the sterilizer isconstructed should be suitable;

b. Another source of error is the ambient background noise. Table 4 ofBS 4196: Part 6 gives correction factors for different levels of backgroundnoise, but the lower the correction factor the more reliable the result willbe. The correction is essentially zero if the background noise level is 10 dBor more below the level measured when the sterilizer is operating. Itshould be possible to achieve this on the manufacturer’s premises if thetest is carried out when the factory is closed and all other plant is shutdown. Steam and compressed air plant not part of the sterilizer should berun on storage during the test, with boiler feed pumps and compressorsswitched off.

Apparatus

E.4 Sound-level meter, complying with type 1 of EN 60651: 1994, or anintegrating-averaging sound level meter complying with type 1 of EN 60804:1994. The sound power level is determined from at least six microphonepositions (Figure E1). If the sound meter has insufficient input channels,additional instruments and/or repeated operating cycles are required.

E.5 Test room, configured so that the distance between any wall or otherobject in the room is not less than 3 m from any reference surface (seeparagraph E.6) on the sterilizer to be tested. The room in which the sterilizer isassembled may be suitable providing the conditions discussed in paragraph E3are met.


Procedures for determining the sound power generated by a sterilizer

Test procedure

E.6 The test determines the A-weighted sound power using a rectangularmeasurement surface. The “reference surface” defined in BS 4196: Part 6 is thesmallest rectangular box that just encloses the sterilizer, with a width and depthmeasured from the outside of the vessel lagging and a height measured fromthe floor to the top of the vessel lagging. The box does not include pipes andvalves used to connect the sterilizer to its services.

E.7 Determine the sound absorption area, A, of the test room using theexperimental method described in A.3.1.2 of BS 4196: Part 6. The method ofestimation described in A.3.1.1 may be used as a check.

E.8 Determine the environmental correction factor, K, as described in A.3.1 ofBS 4196: Part 6. Although EN 285 allows K to be as high as 7 dB, a figure ofaround 2 dB should be achievable as described in paragraph E.3a.

E.9 Sterilizers should be regarded as “large sound sources” as defined in7.4.3.2 of BS 4196: Part 6. The measurement distance, d, should be 1.0 ± 0.1m. Microphones should be placed on the measurement surface as described in7.4 of BS 4197: Part 6. At least six microphones will be required.

E.10 The test is to be carried out with all integral equipment (for example,water pumps, vacuum pumps, compressors) operating normally.

E.11 Load the sterilizer with a full load as described in Part 3 of this HTM. Ifthere is a choice of operation cycle, select the cycle with the higheststerilization temperature. Ensure that the pressure and flow from the steam andwater services are set to levels which cause the maximum noise and are withinthe ranges specified for normal operation. Start the operating cycle.

E.12 Using the procedure for measuring the rectangular measurement surfacedescribed in BS 4196: Part 6, determine the A-weighted sound power level andthe peak sound power level of the sterilizer either for one complete operatingcycle or for a 30-min period that contains the most prominent sounds.

Test result

E.13 Record the calculated mean and peak A-weighted sound power levels indecibels to the nearest integer. Other information should be recorded inaccordance with BS 4196: Part 6.

E.14 The test should be considered satisfactory if the peak A-weight soundpower level at no time exceeds the mean A-weighted sound power level bymore than 15 dB.

Section F

Accommodation for ethylene oxide gas cylinders,

manifolds and canisters


Contents

F.1 General page 183

F.3 Ethylene oxide cylinders page 183F.5 General principles

F.11 Ethylene oxide cartridges page 184


F.0 Accommodation for ethylene oxide gas cylinders, manifolds and canisters

General

F.1 For use in large sterilizers operating at above atmospheric pressure,ethylene oxide is mixed with carbon dioxide or chlorofluorocarbon. Givenrecent concerns about environmental issues however, the use of the latter isdeprecated and is no longer in widespread use. The cylinders therefore are lesshazardous than those of pure ethylene oxide.

F.2 Single-shot cartridges of pure ethylene oxide for use in in sub-atmosphericpressure machines require care but in view of the modest volumes involved donot pose a major safety problem.

Ethylene oxide cylinders

F.3 Cylinders are categorised in accordance with Table F1 and, althoughethylene oxide is supplied in mixture with inert gas, they should be storedunder the toxic and/or corrosive and flammable category.

F.4 Cylinders may be stored with other industrial and medical gas cylinders inaccommodation designed in accordance with HTM 2022.

General principles

F.5 Accommodation should be well ventilated and labelled clearly to describethe gases contained. The labelling should include details of emergency actionprocedures and the location of keys should be identified. Cylinder storageshould be designated as a“no smoking” area and appropriate labels should beposted.

F.6 Clear and secureloading/unloading and

access is required to permit safehandling with vehicular access.

cylinder

F.7 The maximum temperature in the cylinder store should be thatrecommended by the gas supplier/manufacturer. Normally this should notexceed 38°C.

F.8 Accommodation should be free from naked flames and sources of ignitionand appropriate fire extinguishing equipment should be available. Lightingprotection may be necessary for isolated buildings and British Standards CP362should be consulted.

F.9 For electrical equipment in the vicinity of the gas cylinders therecommendations of BS5345: 1976, Zone 2 classification will usually beappropriate for the open-air type of installation.

F.10 Safety equipment in the form of protection goggles, gloves and arespirator should be available inside this space and also at the point of entry.

Previous page is blank

Ethylene oxide cartridges

F.11 Sufficient secure storage within the loading area in the form of a lockedcabinet is satisfactory for cartridges for use in a single day.

F.12 Additional cartridges will be required for an operational unit and externalstorage, for example one week’s supply, should be held externally. Smallspecial-purpose cabins typically used for the storage of LPG containers fullyprotected from the elements will be appropriate.

Table F1 Clarification of gas cylinders typically found on hospital sites

Group classification of Medical gases Non-medical gases

gas cylinder contents

1 Flammable Cyclopropane - this is Acetyleneno longer manufactured LPG (e.g. propane, butane)

STG (synthetic town gas)Methane, natural gas,hydrogen

2 Oxidising and/or Medical compressed air Compressed air oxygen

supports combustion oxygen Nitrous oxideNitrous oxide Oxygen/nitrous oxideOxygen/nitrous dioxide mixturesOxygen/carbon dioxideOxygen/helium mixtures

3 Toxic and corrosive

3.1 Toxic and/orcorrosive and flammable

AmmoniaEthylene oxide (C2H 4O)Carbon monoxideC 2H 4 O/CO 2 mixtures> 6% C2H 4O

3.2 Toxic and/or Nitric oxide mixtures

corrosive and Sulphur dioxide

oxidising Chlorine

3.3 Toxic and/orcorrosive only

Ethylene oxide/halo-carbonmixtures < 15% C2H 4O.Certain conditions only -ethylene oxide/carbondioxide mixtures< 6% C2H4O

4 Others including Carbon dioxideinert, but excluding Heliumtoxic or corrosive

Carbon dioxideNitrogenArgonHeliumHalo-carbonRefrigerants

NHS Estates Library and Information Service1 Trevelyan SquareBoar Lane LEEDS LS1 6AETel: 0113 254 7092/1

References and bibliography

NHS Estates publications

Health Building Note 13. Sterile services department. NHS Estates, HMSO 1992.

Health Building Note 29. Accommodation for pharmaceutical services. Department of Health, HMSO 1988.

HTM 2010. Sterilization. NHS Estates, HMSO 1994, 1995.

British and European Standards

BS6001 Sampling procedures and tables for inspection by attributes.

Part 1: 1991 Specification for sampling plans indexed by acceptable quality level (AQL) for lot-by-lotinspection. AMD 8026, 2/94; AMD 8223, 7/94.

BS6068 Water quality.

Part 6: Sampling.

Section 6.3: 1986(1990) Guidance on the preservation and handling of samples.

Section 6.5: 1991 Guidance on sampling of drinking water and water used for food and beverageprocessing.

Section 6.7: 1994 Guidance on sampling of water and steam in boiler plants.

BS EN 25667 Water quality. Sampling.

25667-1: 1994 Guidance on the design of sampling programmes. AMD 7435, 2/94.

25667-2: 1993 Guidance on sampling techniques. AMD 7436, 8/93.

EN 285 (draft) Sterilization. Steam sterilizers - large sterilizers.

EN 550: 1994 Sterilization of medical devices. Method for validation and routine control of sterilization byethylene oxide.

EN 552: 1994 Sterilization of medical devices. Method for validation and routine control of sterilization byirradiation.

EN 554: 1994 Sterilization of medical devices. Method for validation and routine control of sterilization bymoist heat.

EN 556: 1995 Sterilization of medical devices. Requirements for a device to be labelled sterile.

EN 724 (92/58310/DC) Guidance on the application of EN 29001 and EN 46001 and of EN 29002 and EN 46002for non-active medical devices.

EN 868 Packaging materials and systems for medical devices which are to be sterilized.

EN 868-1 (92/58621/DC) General requirements. Requirements and test methods. Guidance on the use of thisstandard.

EN 868-2 (92/58622/DC) Sterilization wrap - Requirements and tests.

EN 868-3 (92/58623/DC) Paper for use in the manufacture of paper bags (specified in Part 4 of this Standard) andin the manufacture of pouches and reels (specified in Part 5 of this Standard) -Requirements and tests.

EN 868-4 (92/58624/DC) Paper bags - Requirements and tests.

EN 868-5 (92/58625/DC) Heat sealable pouches and reel material manufactured from paper and plastic -Requirements and tests.

EN 868-6 (92/58626/DC) Paper for the manufacture of packs for medical use for sterilization by ethylene oxide orirradiation - Requirements and tests.

EN 868-7 (92/58627/DC) Adhesive coated paper for the manufacture of packs for medical use for sterilization byethylene oxide or irradiation - Requirements and tests.

EN 868-8 (92/58628/DC) Re-usable containers - Requirements and tests.

EN 867 Non-biological systems for use in sterilizers.

EN 867-2 (92/57872/DC) Process indicators (Class A).

EN 980 (93/58310/DC) Terminology, symbols and information provided with medical devices. Graphicalsymbols for the labelling of medical devices.

EN 10411 Terminology, symbols and information provided with medical devices. Information supplied by themanufacturer with medical devices. (Not yet available as draft for comment).

EN 1174-1 (93/507344/DC) Sterilization of medical devices - estimation of the population of micro-organismson product.

Department of the Environment publications

Methods for the Examination of Waters and Associated Materials

Measurements of electrical conductivity and the laboratory determination of the pH value of natural, treatedand waste waters. Department of the Environment/National Water Council Standing Committee of Analysts, HMSO.(out of print)

Atomic absorption spectrophotometry 1979 version. Department of the Environment/National Water CouncilStanding Committee of Analysts, HMSO. (out of print)

The determination of anions and cations, transition metals, other complex ions and organic acids and bases inwater by chromatography 1990. Department of the Environment/National Water Council Standing Committee ofAnalysts, HMSO 1990.

Colour and turbidity of waters, 1981. Department of the Environment/National Water Council Standing Committee ofAnalysts, HMSO. (out of print)

Mercury in waters, effluents, soils and sediments etc, additional methods 1985. Department of theEnvironment/National Water Council Standing Committee of Analysts, HMSO. (out of print)

Lead in potable waters by atomic absorption spectrophotometry 1976. Department of the Environment/NationalWater Council Standing Committee of Analysts, HMSO. (out of print)

Cadmium in potable waters by atomic absorption spectrophotometry 1976. Department of theEnvironment/National Water Council Standing Committee of Analysts, HMSO. (out of print)

Lead and cadmium in fresh waters by atomic absorption spectrophotometry (second edition) - a generalintroduction to electrothermal atomization atomic absorption spectrophotometry 1986. Department of theEnvironment/National Water Council Standing Committee of Analysts, HMSO. (out of print)

Phosphorus and silicon in waters, effluents and sludges 1992. Department of the Environment/National WaterCouncil Standing Committee of Analysts, HMSO 1993.

Iron in raw and potable waters by spectrophotometry (using 2,4,6-tripyridyl-1,3,5-triazine) 1977. Department ofthe Environment/National Water Council Standing Committee of Analysts, HMSO. (out of print)

Iron and manganese in potable waters by atomic absorption spectrophotometry 1983. Department of theEnvironment/National Water Council Standing Committee of Analysts, HMSO. (out of print)

Chloride in waters, sewage and effluents 1981. Department of the Environment/National Water Council StandingCommittee of Analysts, HMSO. (out of print)

General principles of sampling and accuracy of results 1980. Department of the Environment/National WaterCouncil Standing Committee of Analysts, HMSO. (out of print)

Total hardness, calcium hardness and magnesium hardness in raw and potable waters by edta titrimetry 1981.Department of the Environment/National Water Council Standing Committee of Analysts, HMSO. (out of print)

The determination of alkalinity and acidity in water 1981. Department of the Environment/National Water CouncilStanding Committee of Analysts, HMSO. (out of print)

The measurement of electrical conductivity and the laboratory determination of the pH value of natural,treated and waste waters 1978. Department of the Environment/National Water Council Standing Committee ofAnalysts, HMSO. (out of print)

The determination of pH in low ionic strength waters 1988. Department of the Environment/National WaterCouncil Standing Committee of Analysts, HMSO 1988.

Health and Safety Executive publications

Safety in health service laboratories: safe working and the prevention of infection in clinical laboratories.Health and Safety Executive, HMSO 1991.

Steam boiler blowdown systems (Guidance Note PM 60). Health and Safety Executive, HMSO 1987.

Automatically controlled steam and hot water boilers (Guidance Note PM 5). Health and Safety Executive, HMSO1989.

Miscellaneous references

The Rules governing medicinal products in the European Community. Volume IV : good manufacturingpractice for medicinal products. Commission of the European Communities, HMSO 1992.

Guidelines for the safe production of heat preserved foods. Department of Health, HMSO 1994.

International standards for drinking water. Third edition, World Health Organisation, HMSO 1971.

75/107/EEC Directive on the approximation of the laws of the member states relating to bottles used as measuringcontainers. Official Journal of the European Communities, L42, 15/2/75.

80/778/EEC Council Directive relating to the quality of water intended for human consumption. OfficialJournal of theEuropean Communities, 1980.

Alder, VG and Alder, Fl. Preserving the sterility of surgical dressings wrapped in paper and other materials.Journal of Clinical Pathology, vol 14, pp 76-79, 1961.

Biglow, WD. The logarithmic nature of thermal death time curves. Journal of infectious Diseases, vol 29, pp528-536, 1921.

Chick, H. An investigation of the laws of disinfection. Journal of Hygiene, vol 8, pp 92-158, 1908.

Christie, JE. Muslin vs. paper autoclave wrappers - a hospital study. Hospital Topics, Pt 1, vol 35, pp 117-121; Pt 2,vol 35, pp 111-116 (March-April) 1957.

Duncan, MH. Double wrapping - is it really necessary? Journal of the Association of Sterile Supply Administrators,vol 1, no 2, pp 12-14, 1972.

Esty, JR and Meyer, KF. The heat resistance of the spores B. botulinus and allied anaerobes. Xl. Journal ofInfectious Diseases, vol 31, pp 650-663, 1922.

Favero, MS. The dual meaning of heat activation. Spore Newsletter, vol 2, no 12, pp 153-164.

Fallon, RJ. Wrapping of sterilized articles. Lancet, vol II, p 785, 1963.

Finley, N and Fields, ML. Heat activation and heat-induced dormacy of Bacillus stearothermophilus spores.Applied Microbiology, vol 10, pp 231-236, 1962.

Hughes, KEA, Drewett, SE and Darmady, EM. The risk of contamination of sterile dressings packed in paper bags.British Hospital Journal and Social Service Review, vol 77, pp 764-765,781, 1967.

Hunter, CLF, Harbord, PE and Riddett, DJ. Packaging papers as bacterial barriers. Symposium on Sterilization ofSurgical Materials, April 11-13, 1961.

Jevitt, D. Indefinite shelf life . . . Amen! Journal of Healthcare Material Management, vol 2, no 6, pp 36-37, 1984.

Knox, Penikett and Duncan. The avoidance of excessive superheating during steam sterilization of dressings.Journal of Applied Bacteriology, vol 23, pp 21-27, 1959.

Lewith, S. Ueber die Ursache der Widerstandsfähigkeit der Sporen gegen hohe Temperaturen. Ein Beitrag zurTheorie der Desinfektion. Archives Exploring Path Pharmacol, vol 26, pp 341-354, 1890.

Mayworm, D. Sterile shelf life and expiration dating. Journal of Hospital Supply Processing and Distribution, vol 2,no 6, pp 32-35, 1984.

Moates, DW, Dabbah, R and Edwards, VM. Interpretation of non-logarithmic survivor curves of heated bacteria.Journal of Food Science, vol 36, pp 523-526, 1971.

Pflug, IJ and Schmidt, CF. Thermal destruction of micro-organisms: in Disinfection, sterilization and preservation, EdsCA Lawrence and SS Block, pp 63-105, Lea and Febiger, 1968.

Russell, AD. The destruction of bacterial spores: in Inhibition and destruction of the microbial cell, Ed. WB Hugo,Academic Press, 1971.

Shull, JJ, Cargo GT and Ernst, RR. Kinetics of heat activation and of thermal death of bacterial spores. AppliedMicrobiology, vol 11, pp 485-487, 1963.

Speers, R Jr and Shooter, RA. Use of double wrapped packs to reduce contamination of the sterile contentsduring extraction. Lancet, vol II, pp 469-470, 1966.

Standard, PG, Mallison, GF and Mackel, DC. Microbial penetration through three types of double wrappers forsterile packs. Applied Microbiology, vol 26, pp 59-62, 1973.

Sturdy, JH, Baird, RM and Gerein, AN. Surgical sponges: a cause of granuloma and adhesion formation. Annals ofSurgery, vol 165, pp 123-134, 1967.

Walter, CW. Letter on an article ‘An Evaluation of paper used for wrapping articles to be sterilized’ in vol 10,Bulletin of the American Society of Hospital Pharmacists, vol 11, pp 317, 1954.

Other publications in this series

(Given below are details of all Health TechnicalMemoranda available from HMSO. HTMs marked (*) arecurrently being revised, those marked (†) are out of print.Some HTMs in preparation at the time of publication ofthis HTM are also listed.)

1

2

345620078200920111213201420151617

18

19

2020

2021

20222023

202526

2027

Anti-static precautions: rubber, plastics andfabrics.†Anti-static precautions: flooring in anaesthetisingareas (and data processing rooms), 1977.--

Steam boiler plant instrumentation.†Protection of condensate systems: filming amines.†Electrical services: supply and distribution, 1993.-

Pneumatic air tube transport systems, 1995.Emergency electrical services, 1993.--

Abatement of electrical interference, 1993Bedhead services, 1994, 1995.-

Health building engineering installations:commissioning and associated activities, 1978.Facsimile telegraphy: possible applications inDGHs.†Facsimile telegraphy: the transmission of pathologyreports within a hospital - a case study.†Electrical safety code for low voltage systems,1993.Electrical safety code for high voltage systems,1993, 1994.Medical gas pipeline systems, 1994.Access and accommodation for engineeringservices.*Ventilation in healthcare premises, 1994.Commissioning of oil, gas and dual fired boilers:with notes on design, operation andmaintenance.†Hot and cold water supply, storage and mainsservices, 1995.

28 to 39 -2040 The control of legionellae in healthcare premises -

a code of practice, 1993.41 to 49 -2050 Risk assessment in the NHS estate, 1994.51 to 53 -2055 Telecommunications (telephone exchanges), 1994.

Component Data Base (HTMs 54 to 70)

54.15556575859606162636465666768697071

User manual, 1993.Windows, 1989.Partitions, 1989.Internal glazing, 1995.Internal doorsets, 1989.Ironmongery.†Ceilings, 1989.Flooring.*Demountable storage systems, 1989.Fitted storage systems, 1989.Sanitary assemblies.*Health signs.*Cubicle curtain track, 1989.Laboratory fitting-out system, 1993.Ducts and panel assemblies, 1993.Protection, 1993.Fixings, 1993.Materials management modular system.*

72 to 80 -

Firecode

81 Firecode: fire precautions in new hospitals.*81 Supp 1 1993.82 Firecode: alarm and detection systems, 1989.83 Fire safety in healthcare premises: general fire

precautions, 1994.85 Firecode: fire precautions in existing hospitals,

1994.86 Firecode: fire risk assessment in existing hospitals,

1994.87 Firecode: textiles and furniture, 1993.88 Fire safety in health care premises: guide to fire

precautions in NHS housing in the community formentally handicapped/ill people, 1986.

New HTMs in preparation

2024 Lifts2030 Washers for sterile production

Health Technical Memoranda published by HMSO can bepurchased from HMSO bookshops in London (post ordersto PO Box 276, SW8 5DT), Edinburgh, Belfast,Manchester, Birmingham and Bristol, or through goodbooksellers. HMSO provide a copy service for publicationswhich are out of print; and a standing order service.

Enquiries about Health Technical Memoranda (but notorders) should be addressed to: NHS Estates, Departmentof Health, Marketing Unit, 1 Trevelyan Square, Boar Lane,Leeds LS1 6AE.

About NHS Estates

NHS Estates is an Executive Agency of the Department ofHealth and is involved with all aspects of health estatemanagement, development and maintenance. The Agencyhas a dynamic fund of knowledge which it has acquiredduring 30 years of working in the field. Using thisknowledge NHS Estates has developed products which areunique in range and depth. These are described below.NHS Estates also makes its experience available to the fieldthrough its consultancy services.

Enquiries about NHS Estates should be addressed to:NHS Estates, Marketing Unit, Department of Health,1 Trevelyan Square, Boar Lane, Leeds LS1 6AE.Telephone 0113 254 7000.

Some other NHS Estates products

Activity DataBase - a computerised system for definingthe activities which have to be accommodated in spaceswithin health buildings. NHS Estates

Design Guides - complementary to Health BuildingNotes, Design Guides provide advice for planners anddesigners about subjects not appropriate to the HealthBuilding Notes series. HMSO

Estatecode - user manual for managing a health estate.Includes a recommended methodology for propertyappraisal and provides a basis for integration of the estateinto corporate business planning. HMSO

Concode - outlines proven methods of selecting contractsand commissioning consultants. Reflects official policy oncontract procedures. HMSO

Works Information Management System - acomputerised information system for estate managementtasks, enabling tangible assets to be put into the contextof servicing requirements. NHS Estates

Health Building Notes - advice for project teamsprocuring new buildings and adapting or extendingexisting buildings. HMSO

Health Guidance Notes - an occasional series ofpublications which respond to changes in Department ofHealth policy or reflect changing NHS operationalmanagement. Each deals with a specific topic and iscomplementary to a related HTM. HMSO

Printed in the United Kingdom for HMSODd 300377 3/95 C15 5600 35335

Health Facilities Notes - debate current and topicalissues of concern across all areas of healthcareprovision. HMSO

Firecode - for policy, technical guidance and specialistaspects of fire precautions. HMSO

Capital Investment Manual Database - softwaresupport for managing the capital programme. Compatiblewith the Capital Investment Manual. NHS Estates

Model Engineering Specifications - comprehensiveadvice used in briefing consultants, contractors andsuppliers of healthcare engineering services to meetDepartmental policy and best practice guidance. NHSEstates

Quarterly Briefing - gives a regular overview on theconstruction industry and an outlook on how this mayaffect building projects in the health sector, in particularthe impact on business prices. Also provides informationon new and revised cost allowances for health buildingsPublished four times a year; available on subscriptiondirect from NHS Estates. NHS Estates

Works Guidance Index - an annual, fully cross-referenced index listing all NHS Estates publications andother documents related to the construction andequipping of health buildings. NHS Estates

Items noted “HMSO” can be purchased from HMSOBookshops in London (post orders to PO Box 276,SW8 5DT), Edinburgh, Belfast, Manchester,Birmingham and Bristol or through goodbooksellers.

NHS Estates consultancy service

Designed to meet a range of needs from advice on theoversight of estates management functions to a muchfuller collaboration for particularly innovative or exemplaryprojects.

Enquiries should be addressed to: NHS EstatesConsultancy Service (address as above).

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